>> We will get started with the open session of the 27th meeting for the national Center for the -- Advisory Council day one and will have another set of meetings tomorrow, Day 2. And so for now I am going to gavel us in for the session ticket is rolling. (Gavel) We are convened. --- I want to welcome you all And before we get started taking a quick roll call. I am going to start listing everybody's names. And have you confirm that you are here so I'm going to start with Paul Harris. >> -- I'm here. >> Great, hi Paul. Ted Holman. >> Present. >> Matthias Pressler. >> Present. >> Andrew -- >> Hi, I'm here. >> We cannot hear Joanie any more. >> Sorry about that. >> Marshall summer. >> Here. >> George Friedenberg. >> Here. >> Really appreciate the ad hoc nominees attending today too. It's wonderful to have you participate in the discussion over the course of this counci. Okay also, joining us today are a few ex officio members, Frank are you there? >> Hi. >> (indiscernible). >> Here. >> Great. And Rita Ramoni (phonetic). (correction)Rachel. >> Rachael may not be on yet we will check into that. She may not be able to make it for a little bit so we will move on. I think that gives us a full roster for this meeting and we are ready to move forward and I just want to go ahead and review the agenda for the meeting. --- As you can see the open session council will take place over two days and I'm going to present the director's report right after some of these opening remarks, and then the next will be program updates from the division of preclinical innovation by director Anton -- And we will review the agenda for tomorrow. Tomorrow will be primarily about clearance of concepts, that will be a full agenda and now I would like to turn over to Anna who will briefly go over the logistics of this meeting so you will be aware of that as well as future meeting dates. Anna over to you. >> Today we are using a Zoom platform and all of the members are participating as panelists, and you're free to speak and we ask however that you either use the raise hand or chat feature and wait to be called upon so we can have an orderly session please allow the speakers to move through the presentation. And then we will ask you to present when you are called. We are also using videocast today. Audience members who are non-councilmembers or non-staff may submit emails available on the NIH site. You can also send in emails listed on the slide, and the feedback sends the email to the same address and that is the Method to collect public comments today. We need to consider the minutes of the January 2021 meeting. May I have a motion to approve the minutes please? >> Motion moved. >> Second. >> All in favor? >> Aye. >> Aye. >> Aye. >> Any abstentions? Without the minutes of the January 2021 advisory Council session are approved. --- As you can see the future meeting dates for the advisory Council on the slide and we will be meeting two days in September on the 23rd and 24th using a virtual platform and we will be back in person in 2022 and 2023. . With that I would like to turn it over to our director. >> DR. RUTTER: Thank sso much Anna. My title slide is to give you the director's reports, Things that have been happening since we last met and to start off I get the distinct honor and pleasure of introducing our NCATS new official council members. Forgive me for not relying complete bios for each of you but I can set our council is top-notch when You hear your name please put yourself on camera and waves of people can see you. In alphabetical order we have Paul Harris, a professor in the Department of biomedical informatics and biomedical engineering at Vanderbilt University Medical Center in Nashville Tennessee. We have Matthias Kretzler, at Ann Arbor Michigan. Keith Mueller Professor department head at the department of health management and policy in Iowa city, IA. --- We have Paula Shireman, Professor in the Department of surgery, microbiology and immunology, and molecular genetics at the University of Texas health science Center. Marshall Summar, Professor and Director of the rare disease Institute, division of genetics and metabolism, children's National Medical Center. --- When September rolls around I hope that we can introduce you as full members at the time. Welcome everyone. --- This is our first counsel for many of us including me so I'm going to take this opportunity to introduce myself, a little more than I probably would do otherwise and I will also introduce you to NCATS. My degree is in pharmacology and I have been involved In a variety of programs throughout my career and the most frustrating part for me over the course of my career has been thinking about how we get from A to B, and in my case it spending a lot of time finding genes that contribute to disease and that is good but it's not sufficient. It's really understanding sort of this arrow between A and B that has been most interesting to me and that is where you find the why and the how in the insight you gain and how to fix it when it goes awry and how to get it most effectively and efficiently, so that is a little bit about me in my professional life. --- And I'm going to tell you my personal story, this is a photo of me and my mother. Her name was Dorothy and yes we are all from a small town in Kansas. My mother had a rare disease called Myelofibrosis, it took about 15 years to be diagnosed and when she was I found a doctor experience with a disease and back then it was not easy to find and as it turns out that physician was and still is the Mayo Clinic and now he is very easy to find through the NCATS website or the NORD website where you can find physicians associated with particular rare diseases, very important thing for the rare disease community. And at the time of treatment there were only clinical trials and that required her to travel over great distances and alone, and she was not willing to pay that price so understanding the plight of a rare disease patient for the diagnostic Odyssey and waiting for the treatment options and only have those options be very difficult to access is a story that is exhausting and I have a dedication to finding ways to improve all of these factors and I know I am not alone in that sort of sentiment and that is a lot of what we do here at NCATS. --- And on top of her rare to see she also had a much more common one and heart disease. --- This is from our whirlwind data. And if you look at the past 30 years of the burden of diseases, Looking at how many years of life lost due to the premature disability from the disease, if you follow this overtime it not only has not changed all that much despite more tools and technologies; Is also trending in the wrong direction. Dailies are increasing. --- In addition to this, we think that there are about 10,000 diseases and most of them are rare; current estimates are that there are about 7000 rare diseases affecting about one in 10 Americans, about 30 million people and for a long time what has been my life's work is that researchers have In figuring out what genes cause what diseases and there has been tremendous success in that work but what has been much slower as I mentioned before is translating that knowledge that a gene causes a disease into finding a treatment for that disease. --- So in fact only about 500 of all diseases have a treatment, that is 95 percent that don't; So knowing the gene is about the first of many steps needed to consider how to develop a treatment and Thinking about doing this on the scale of over 10,000 diseases is very daunting to say the least we need to do something different. --- So our mission at NCATS is to turn promising research discoveries into solutions through translational science. The NCATS approach to present each stage of research along the path through preclinical approaches to biological steps two approaches that improve the health of individuals in the public and although this is rarely linear or unidirectional as depicted here, NCATS develops new approaches and demonstrate usefulness and disseminates their findings. And inclusive of this are two main things I want to point out: we must find ways to hear from people who are affected by the diseases. That need therapeutic solutions. And secondly health inequity is a structural issue that must be addressed, we cannot stop at developing therapies we must continue to raise awareness about rare diseases and inequities and common diseases within populations of color, access to care, training the next generation someone. So with this our driving hope is to bring more treatments to more people, more quickly and making one edit here: For ALL peple, more quickly. --- How does NCATS do it? Every project is about translation, it has to advance the size of the project for example moving a project from preclinical development to phase 1 clinical trial is depicted here, and it has to identify and address costly and time-consuming bottlenecks that slow down or prevent the translation of the research as depicted by these purple blobs inside the pipeline. --- If you think about the pipeline with the flow from A to B, things go in and things come out and the flow is determined by the openness of the pipe but these purple blobs represent the idea that pipes have bottlenecks. These are things that can slow down the translational research like operational bottlenecks or financial or administrative factors, or scientific issues for example. And that is why they are in our purview to address; we pay close attention to these to figure out how to address them because we have four arrows going in at the beginning and we do not want to be in a position where only one comes out, slowly trickling out of the pipeline. In fact we want to increase the pace of testing and treatment for many diseases at the time and we want all four errors to come out, full bore in the translational science process. --- So this is the NCATS way. We want to understand the process. And the easier it is to get from A to B, and then the more predictive it becomes but in reality is a lot more complex Than the Chevron pipeline I am showing. If you look under the hood of each block, We detail the broader specific activities underlining each step, and this is called the 4DM, or the drug discovery, development and deployment map for enhance usability and interactive experience in the sections color-coded So you know where you are in the map And users can zoom in and out Of areas they are interested in, find best practices and find information and connect with relevant NCATS program staff and resources. --- Although it is daunting that there are a lot of processes underlining the translation process it is not insurmountable if you know where you are and you know what you're going and you know what to do next and identify collaborators along the way who have expertise along the way. This was developed through a collaborative effort among the action collaborative of the forum on drug discovery, development and translation of the National Academy of Sciences engineering in medicine has been an incredibly useful tool to have in our toolkit. --- So this is the NCATS way, bringing together stakeholders that have not talked to each other before and patience in finding this cross collaboration and partnerships and identifying transformative stakeholder engagement, developing robust platforms and technologies finding ways to be productive and risk-taking to remove the scientific and operational barriers And I'm going to give you a sense of how we do this for the remainder of the talk. --- Now, within NCATS we can start to chip away at the big operational and scientific challenges with this approach; these are challenges that have built up over time And there will always be challenges as we go forward But some of the operational roadblocks we encounter Are in the areas of education and training Part of an effort to fill needs To getting more people involved in the translational science and bringing learnings to their own background. Or perhaps data transparency in IT management for example, other operational barriers. They may not be compatible but have to be in an environment of team science which is critical to the success of NCATS. They must be unabated for progress. --- The other major piece in translational science Are things like predicting human toxicity and efficacy from the pre-clinical perspective are encouraging and establishing better data interoperability and strengthening our clinical research and trial Infrastructure. So these are some of the examples of the challenges that we face. --- And of course structure in a way that enables our function and we have a leadership for setting up the vision not only for NCATS but to the broader NIH activities as well like the Covid response in the Council and the -- board are also part of this response. (Addressing org chart). At the bottom here are more outward facing programs, scientific programs that provide oversight to conduct all scientific and programmatic activities from preclinical innovation to strategic initiatives, to drug development partnerships, to rare disease research and clinical innovation. These are highly integrated teams that require constant interaction so don't let this hierarchical graphic display fool you. And over the course of Your term on council you will have a chance to hear more about the work that these groups do. --- As you can tell from our mission statement NCATS is not about one disease, it is about all diseases and here we use two main translational science approaches. On the left everything we do is a collaboration. We say that translational science is a team sport; We have the expertise and technological capacity to cover the breadth of of the preclinical space. The second thing that we do on the right is a development of platforms, tools and resources to port these activities in both of the strategies help us save time, lower costs and get more therapist emergencies is faster, and I hope you are sensing a theme here. --- Collaborations are the lifeblood of NCATS, but not easy to negotiate so it turns out that NCATS is reduce the time from an idea to an agreement, to the development of a template agreements to get things done faster. These are designed to streamline the legal and administrative processes for partnering across multiple organizations and provide a roadmap for handling intellectual property, publications and things of that nature. And so now we can go from idea to agreement in about three months where before it took about 9-12 months, so this is been truly catalytic for establishing collaborations and partnerships for what we do. --- And because collaborations are our lifeblood everything that I mentioned today is representative not just of NCATS but many of the public and private partners and collaborators along the way. --- So I'm going to transition out of some examples of the scientific questions that we are tackling. And going back To the translational pipeline you can think about that in your head there tends to be a high failure rate of projects around stages of preclinical development that has plagued us for quite some time. --- A couple of major challenges are that it takes about 10-15 years to bring a drug to market with an average cost of about 2.6 billion dollars. And the kicker here is that there is a 90 percent failure rate, mostly due to the lack of efficacy and 28% due to the lack of toxicity and some of the business considerations, like losing interest in the project for example in this is why we refer to preclinical spaces covering the Valley of Death. --- A key to the failure is relying on one-size-fits-all approach; animal model particularly mouse models Conform investigation drugs to humans, and we need to change this because mice do not represent humans well. --- We need to also make sure that we are not entrenched in this failure; we need new technologies and better predictive tools. So what this means is that we need to move beyond low definition culture and better model the physiological complexity of humans. To that and we have developed organoids, 3D model systems in tissue culture, and better tools to get at this disease complexity and of course this is a double edge sword Because as you gain the physiological complexity and as you move for the right-hand side Of his visual you lose some of that high throughput screening capacity So we need to balance these two sides, but there is no question that Better human cell tissue, organ based models are needed to speed up that 10-15 window that it takes to develop a drug. One of the recent findings has to do with induced pluripotent stem cells. Cells can be taken for patient's blood and reversed engineered to become pluripotent stem cells, and this can serve as an inexhaustible resource for iPS cells, but stem cells are sensitive and their use is hampered by trying to grow them in culture dishes, and we can damage the DNA and they are not viable to be used more reproducively in these types of testing. --- What our researchers found was a cocktail of compounds that did exactly that, the cocktail is called CEPT, made up of these regions on the left, chroman 1, emricasan an inhibitors that prevent cell death, polyamines survival agents, and there is something called trans-ISRIB, trance integrating stress response inhibitor and it does exactly what you might think it does. These four agents are transforming our ability to work with these important cells and we are not able to work with these in tissue culture cryo preserve them bring them out to do a variety of new activities like gene editing or building organids, things of that nature. --- Here are some of the data underlying the work done at the labs; they start reagents used to stabilized the cells along the path here on the left in the yellow box, we stained the cells to show these markers of viability. And these agents listed above, the DMSO and Y-27632 have been used in the past but they are good, but not great. We need to find something that works 11 better and on the right-hand side in the blue box you see happier cells with the CEPT cocktail and we expect this to be an advancement in the field to use the self more reliably. Lots of work to do here but this is a fantastic start. --- So going back to this picture, we can use the IPSC primary cells to construct 3D cellular models to get at how to make the preclinical drug development more producible and more predictive, and I'm going to highlight two of these models. To increase predictability we use 3D printing to increase the cellular and physiological complexity in these 3D tissue models that recapitulate the relevant environment found in the bodies rather than the red/green/yellow ink you using your printers, we use cells. We built issues and engaged disease experts to make sure we recapitulate the disease characteristics in the model and then we screen for compounds that might reverse the disease state. >> On As we think about 3D models, this is showing -- used in the bio fabrication of skin tissue shown on the left. We use dies look at different expressions to validate this model and turned south at this model is quite robust for something called atopic dermatitis; another team within the NCATS labs shows that a clinical relevance of these tissue models to correct disease phenotype attesting effects of clinical drugs for atopic dermatitis. You can see a difference between what normal looks like and what atopic dermatitis looks like and you can see the barriers between the cell layers that are not quite well-formed in atopic dermatitis. >> RESTORE FROM THE DISEASE STATE TO A NORMAL STATE THE CONTACT ON THE RIGHT ACTUALLY RESTORES TO THE NORMAL STATE HERE. THIS IS IT THE KIND OF WORK WE CAN TWO WITH 3-D TISSUE MODELS. AS WE GET INTO APPROACHES LIKE TISSUE CHIPS, THE SKY'S THE LIMIT. THIS IS MOSTLY AN EXTRAMURALLY FUNDED PROGRAM OUT OF THE OFFICE OF STRATEGIC INITIATIVES THAT STARTED ABOUT SEVEN, EIGHT YEARS AGO AND HAS MADE INCREDIBLE PROGRESS. GOING BACK TO THE IPS CELLS I TOLD YOU ABOUT BEFORE YOU CAN TAKE PATIENT CELLS AROUND DERIVE THEM TO LUNG CELLS AND PUT THEM ON A CHIP FOR A MORE NATIVE ENVIRONMENT LIKE OUR LUNGS DO. AND TISSUE CHIPS ARE NOW COMMERCIALLY AVAILABLE FOR A VARIETY OF TISSUES AND ORGANS. THE NEXT STEP WE'RE EMBARKING ON AND LOOKING AT CLINICAL APPLICABILITY SUCH AS CLINICAL TRIALS ON A CHIP AND WE CAN PUT THE HEART AND LUNG AND KIDNEY OR LIVER ON THE SAME CHIP AND LOOK AT VASCULARIZATION TO GIVE A SENSE OF YOU ON A CHIP. WE'RE WORKING HAND IN GLOVE WITH THE FDA TO THINK OF REGULATORY APPROACHES IN THIS CASE TOO. THIS ISN'T ROCKET SCIENCE BUT WE USE ROCKET SCIENCE FOR THIS AND WE CAN LOOK AT A VARIETY OF DISEASES AND CONDITIONS IN A SHORT TIME FRAME. WE LAUNCHED OUR RECENT BATCH OF TISSUE CHIPS LAST WEEK. ONE OF THE ADVANCES PARTNERSHIP WITH NASA WAS THE MINIATURIZATION OF THE TISSUE CHIPS WHERE NASA SCIENTISTS HELP US IMPROVE THE TECHNOLOGY FASTER TO DO EXPERIMENTS IN THE SPACE STATION REQUIRED VERY SPECIFIC REQUIREMENTS TO FIT IN THE ISS. FROM THE NASA PERSPECTIVE IT HELPS UNDERSTAND THE MICROGRAVITY ON THE ASTRONAUTS AND PERHAPS ON MARS ON VENUS AND HOW MICROGRAVITY AFFECTS LIFE ON EARTH AND WHAT HAPPENS IN SPACE IS WHEN ASTRONAUTS ARE IN SPACE THEY EXPERIENCE BONE DEMINERALIZATION OR KIDNEY PROBLEMS AND SO OUR GOAL IS TO REALLY USE THIS MICROGRAVITY ENVIRONMENT TO UNDERSTAND HOW TO LOOK AT THESE TYPES OF DISEASES BACK HERE ON EARTH. SO THIS SAY REALLY IMPORTANT PROGRAM FOR US. I TALKED ABOUT THE PRECLINICAL SPACE AND IF WE APPROACH A ONE DISEASE AT A TIME BASIS WE'LL BE WAITING THOUSANDS OF YEARS FOR TREATMENT FOR ALL AND WITH THE OFFICE OF RARE DISEASE AND SEVERAL NIH PARTNERS INCLUDING NINDS AND OTHERS HAVE BEEN GREAT PARTNERS IN THIS WORK TO MOVE THIS TYPE OF SCIENCE I'LL BE TALKING ABOUT HERE. SO WE KNOW BEFORE 80% OF RARE DISEASE CAUSED BY A SINGLE GENE MUTATION. IF THAT'S THE CASE THEN GENETIC MUTATIONS ARE THE COMMON THREAD AND INSTEAD OF GENE BY GENE WE USE OTHER APPROACHES ON WHO IS COMMON AND HOW DO WE SEEK TO REPLACE THE DEFECTIVE GENE WITH THE FUNCTIONAL ONE? WE'RE USING THREE APPROACHES I'LL OUTLINE. THE FIRST I'LL SHOW IS PLATFORM VECTOR GENE THERAPY OR GENE THERAPY APPROACH. REPLACING A DISEASE CAUSING GENE WITH A FUNCTIONAL IS ONE AND WE'RE LOOKING AT ONE PARTICULAR VECTOR CALLED ABNO ASSOCIATED VIRUS 9 AND USING A SINGLE MANUFACTURER WITH OUR NIH TEAMS AND HOPE IF YEAR SUCCESSFUL IN THIS GOAL WE'LL BE ABLE TO SPEED RESEARCH FOR MANY DISEASES AT ONE TIME AND I'LL TELL YOU ABOUT A FEW OTHER STRATEGIES WE'RE EMBARKING ON AS WELL. SO GENE EDITING IS ANOTHER ONE. IT'S ESSENTIALLY CHANGING OUT THE PIECE OF THE DNA CAUSING THE DISEASE. AND HERE WE'RE EXPANDING THE GENE EDITING TOOLS TARGETING DIFFERENT DELIVERY SYSTEMS TO SEE WHICH ONES WORK AND DEVELOPING ASSAYS FOR SAFETY AND EFFICACY AND DISSEMINATING THE RESOURCES FOR THE RESEARCH COMMUNITY. NEXT IS CALLED OLIGONUCLEOTIDES AND THIS IS ANOTHER APPROACH THAT FITS IN OUR REPERTOIRE. WE'RE DEVELOPING THE ASO DRUGS TO UNDERSTAND TOXICOLOGY AND HOW THEY WORK IN THE CELLS AND A GENE WE'RE WORKING ON IS KIF5A AND HEAVY CHAIN ISO FORM 5A AND THAT CAN TREAT A VARIETY OF DIFFERENT DISEASES THEORETICALLY. THIS ARE EXAMPLES OF THINGS WE'RE DOING IN PARALLEL TO SEE IF WE CAN MANAGE MORE THAN ONE DISEASE AT A TIME APPROACH. I MENTIONED THE GENE THERAPY FIRST AND I'LL TELL YOU MORE ABOUT THAT. ONE IS TO USE THE ADENO-VOESHT ADENO-ASSOCIATED VIRUSES AND THEY DO NOT CAUSE THE DISEASE BUT HOLD GREAT PROMISE FOR MANY DISEASES. THIS IS WHAT THE VIRUS LOOKS LIKE. IT'S ESSENTIALLY A CARTOON BUT PERHAPS THIS MIGHT SHOW IT A LITTLE BIT BETTER. THE AAV GENE THERAPIES USE A MODIFIED VERSION OF THE VIRUS. ESSENTIALLY WE CAN TAKE OUT THE VIRAL DNA FROM THE SURROUNDING SHELL IT'S IN AND WE INSERT A WORKING COPY OF THE DEFECTIVE GENE INTO THE CAPSID AND LET THE VIRUS DO WHAT IT'S GOOD AT, INFECT THE CELLS AND INJECTS THE DNA INTO THE CELL. HERE'S THE CATCH. WE MADE THE VIRUS INFECT CELLS WITH GOOD COPIES OF THE DEFECTIVE GENES SO WHEN IT INFECTS THE CELL WITH THE GOOD COPIES THE CELL TAKES OVER WHAT THEY DO BEST, MAKING THE RIGHT PROTEINS AND MACHINERY FOR LIFE. SO THIS IS REALLY WE THINK A VERY EFFECTIVE PROCESS AND WE'RE TESTING THIS OUT NOW AS WE SPEAK ON A VARIETY OF RARE DISEASES I'LL GIVE A SENSE OF HERE. THERE'S FOUR DISEASES, TWO ORGANIC ACIDEMIAS AND THE DISEASE GENES AT TOP THAT CAUSE ORGANIC CASES AND THOSE LISTED AND DOING THE STUDY IN THE MIDDLE TO GET THESE TO THE CLINIC FOR PHASE 1 TEST AT THE CLINICAL CENTER WITH OUR PARTNERS AT NINDS AND NHGRI. WE'RE VERY EXCITED ABOUT THIS PROGRAMMING. WE'RE CURRENTLY IN THE MIDST OF THIS IN THE MIDDLE STAGE. IF THESE ASTART TO WORK THEN WE'RE BACK TO WHERE WE STARTED. OUR HOPE IS TO GET MORE TREATMENTS TO MORE PEOPLE MORE QUICKLY. THIS IS ASPIRATIONAL BUT MAYBE BY 2035, IT'S NOT OUT OF THE REALM OF POSSIBILITY WE'LL MAKE A DENT IN HAVING MORE TREATMENTS FOR MORE DISEASES OVER THAT TIME PERIOD. SO FOR THE MOST PART WE'VE BEEN TALKING ABOUT RARE DISEASES NOW BUT ONE OF THE MAJOR POINTS I WANTED TO SAY TOO TO CLOSE OUT THE SESSION IS WHEN STUDYING RARE DISEASES THE ADDITIONAL OPPORTUNITY IS TO APPLY THESE TO THE MORE COMMON GENETICALLY COMPLEX DISEASES AND WHO KNOW WHERE THE PURPLE BAR MAY BE BUT HOPE IT'S AS HIGH AS WHERE I'M SHOWING IT NOW. NOW I WANT TO TRANSITION TO TELL YOU A LITTLE BIT MORE OF WHAT'S HAPPENED MORE URGENTLY IN THE LAST 15 MONTHS WHEN THE PANDEMIC HIT. WIN THE NCATS APPROACH WE'RE BRINGING EVERYTHING WE HAD TO BEAR ON COVID-19. EVERY PICTURE HERE RELATIVE HUMIDITIES A MAJOR PROJECT THE NCATS COMMUNITY -- PICTURE HERE BRINGS TO BEAR WHAT NCATS COMMUNITY HAD TO DO AND DOING SCIENCE AND I SHOULD SAY THIS IS REALLY REPRESENTING SOME OF THE NCATS WORK DONE BY THE COMMUNITY BUT ALSO THERE'S BEEN A TREMENDOUS AMOUNT OF WORK ACROSS THE SCIENTIFIC LANDSCAPE AND THIS HAS BEEN JUST A TREMENDOUS EFFORT. SO I'M GOING TO JUST PICK ON SOME OF THESE EXAMPLES HERE. ONE OF THE THINGS WE DID FROM OUR NCATS LABS OUT OF THE GATE WAS TO DEVELOP ASSAYS FOR HIGH THROUGHPUT SCREENING. WE RAN AS MANY SCREENS AGAINST AS MANY COVID TARGETS AS WE COULD FIND AND SCREENED THESE AGAINST ALL THE APPROVED DRUGS WE HAVE IN THE NCATS LABS. WE HAVE A PHARMACEUTICAL COLLECTION CONTAINING OVER 3,000 FDA APPROVED COMPOUNDS. THIS WAS VERY WORTHWHILE TO DO IN TERMS OF SCREENING BECAUSE WE ALREADY KNOW A LOT ABOUT THE COMPOUNDS. THEN WE TOOK OUR DATA AND MADE THEM IMMEDIATELY AVAILABLE FOR THE WORLD TO SEE AND TO USE AND PERHAPS EVEN RUN AN ANALYSIS. THIS WAS A HUGE TEAM EFFORT FOR EVEN BUILDING THE OPEN DATA PORTAL WITH SCIENTISTS, MATHEMATICIANS AND THOSE AT NCATS WHO WORKED HARD TO MAKE THE RESEARCH AVAILABLE TO QUICKLY. ON THE SITE AS WELL IF YOU'RE INTERESTED IN LOOKING AT IT, THERE'S A WEALTH OF INFORMATION ABOUT THE VIRUS AND ALL THE VARIANTS YOU'VE HEARD ABOUT IN THE NEWS. THROUGH THE ACCELERATING COVID THERAPEUTIC INTERVENTIONS AND VACCINES OR ACTIV. IT'S A PUBLIC-PRIVATE PARTNERSHIPS AND THEY'VE BEEN ABLE TO TEST THERAPEUTICS AGAINST THE VARIANTS AND PROVIDE OPEN ACCESS TO THE DATA . SPEAKING OF DATA, AN ISSUE WAS WRANGLING DATA FROM INDIVIDUALS. IT'S A BIG BOTTLENECK FOR THE RESEARCH COMMUNITY. IN THE UNITED STATES WE DON'T HAVE A STANDARD PROCESS TO COLLECT AND MANAGE ELECTRONIC HEALTH RECORDS. WE DON'T HAVE A STANDARD WAY TO USE PATIENT EHR DATA FOR RESEARCH TO HELP MAKE PUBLIC HEALTH DECISIONS IN NEAR OR REAL TIME USING THE DATA. THEY'RE SILOED OR IN FORMATS NOT COMPATIBLE AND THESE ARE PROBLEMS WE'VE BEEN TRYING TO ADDRESS. THROUGH COLLABORATIONS ACROSS THE CPSAs AS WELL AS THE CLINICAL AND TRANSLATIONAL RESEARCH AWARDS AND THE CENTER FOR DATA HEALTH ALONG WITH THE NCATS COLLABORATORS WE'VE CREATED WHAT'S CALLED THE NATIONAL COVID COHORT COLLABORATIVE. IT'S A SECURE NATIONAL RESEARCH OF PEOPLE WHO TESTED POSITIVE OR NEGATIVE FOR COVID-19. AND OUR GOAL IS THIS WILL SPEED COVID-19 RESEARCH AND IMPROVE PATIENT CARE. IF YOU WERE TO LOOK AT THE DASHBOARD ON THE LINK I SHOWED HERE, THIS A PUBLIC-FACING DASHBOARD AND SHOWS SOME OF THE VACCINE DATA, DATA CONTRIBUTORS AND COMORBIDITY DATA AS WELL. WE HAVE OVER 2 MILLION COVID POSITIVE AND THERE'S A LOT OF DATA TO THROUGH HERE AND WE'RE HOPING THIS WILL ADD VALUE NOT ONLY FOR THE CURRENT PANDEMIC BUT AS WE GO INTO STUDYING LONGER TERM AFFECTS OF THE PANDEMIC. A HUGE BARRIER TO CLINICAL DATA RESEARCH IS INNER OPERABLE. THAT'S THE BIG WIN. WHEN WE BRING DATA IN FROM ELECTRONIC HEALTH RECORDS IT'S COMES IN DIFFERENT FLAVORS. HEIGHT DATA IS IN INCHES IN SOME PLACES AND OTHER PLACES CENTIMETERS. IT DOESN'T MATTER WHAT USED FOR THE DATA MODEL BUT TO COMPARE APPLES TO APPLES WE NEED TO PICK ONE SO THE ANALYSIS CAN BE AS ROBUST AS POSSIBLE. HERE ON THE RIGHT SIDE WE SHOW ALL THE THINGS GET MAPPED TO SOMETHING CALLED OMOP DATA AND I MENTION HEIGHT BUT IF YOU CAN THING OF OTHER VARIABLES YOU MIGHT IMAGINE THESE CAN GET COMPLEX. THE MAPPING FUNCTION AND HARMONIZATION HAS BEEN A BIG EFFORT ON THE COMMUNITY WORKING ON THIS. I SHOULD ALSO SAY ALL THESE DATA CAN NOW ONLY BE MAPPED ON THE ONE DATA MODEL BUT WE MAPPED IT TO A VARIETY OF OTHER DATA MODELS IMPORTANT FOR WORK DONE AT THE FDA. THEY USE A PARTICULAR DATA MODEL CALLED C DISK AND WE'RE INTEROPERABLE WITH THAT MODEL AND FHIR FOR INFORMATION FOR EXCHANGED. IT'S BEEN A HUGE WIN FOR THE COMMUNITIES. RIGHT NOW THERE'S OVER 1,000 RESEARCHERS WORKING ON THIS ENCLAVE TO GAIN MORE INSIGHT INTO COVID. BE ON THE LOOK OUT FOR OTHER FINDINGS TO COME FROM THIS PARTICULAR WORK. ANOTHER CTSA EFFORT WAS CONTRIBUTING TO THE COMMUNITY ENGAGEMENT ALLIANCE AGAINST COVID-19 DISPARITIES. THIS IS SOMETHING CALLED SEAL. THIS WAS LARGELY RUN OUT OF THE NHLBI I.C.s AT THE NIH AND A HUGE LIFT WAS THROUGH THE CTSA PROGRAMS AND THOSE THAT CONTRIBUTED ARE SHOWN IN PURPLE. THEY'VE BEEN INSTRUMENTAL IN HELPING WITH OUTREACH TO ENSURE WE RAISE AWARENESS AMONG THE COMMUNITIES HARDEST HIT BY THE PANDEMIC. SIMILARLY THE TRIAL INNOVATION NETWORK AND RECRUITMENT INNOVATION CENTER WAS RIGHT IN THE MIX ON THE EFFORT AS WELL AS THE ACTIVE CLINICAL TRIAL NETWORK DEVELOPING TOOLS WITH TRANSLATION INTO SPANISH. THIS GROUP HAS BEEN RESPONSIVE TO THE COVID-19 PANDEMIC AND GRATEFUL FOR THE WORK THEY'VE DONE. AND CTSAs HAVE BEEN IMPORTANT AND THESE ARE THE CLINICAL TRIALS HAVE BEEN IMPORTANT AND ACTIVE 1 IS MODULATORS AND 6 IS REPURPOSED DRUGS. PART OF THE ACTIVE PUBLIC-PRIVATE PARTNERSHIPS SHOWN BEFORE. THESE WERE NOT SUPPORTED PER SE BUT ASSOCIATED AND DONE WITH THE FEDERAL SUPPORT WE HAD FOR DOING THESE PARTICULAR TRIALS. ENROLLMENT HAS BEEN CLOSED AND LOOKING FORWARD TO THE TRIALS AND ACTIVE 1 IS ONGOING AND ACTIVE 6 STARTED RECENTLY. WE'RE EXPECTING TO HEAR MORE. WE COLLECTED LESSONS LEARNED AS WE'VE GONE ALONG AND INFUSED THEM FOR THINKING ABOUT OUR PROGRAMS AND SOME OF THE OVERARCHING EXAMPLES THAT WE'VE ESTABLISHED OVER THIS PERIOD ARE SHOWN HERE. I THOUGHT IT WAS IMPORTANT TO SHARE SOME OF THESE THINGS WE FOUND AN OVERARCHING PRINCIPLE FROM THE TIME WE'VE HAD WITH THE COVID PANDEMIC AND THE WORK WE'VE DONE. THE FIRST AMONG THESE ARE TO BE FLEXIBLE. THESE ARE URGENT CHALLENGES AND THEY HAVEN'T BEEN AT THE SAME TIME. THEY'VE BEEN IN WAVES ACROSS THE COUNTRY. WE NEED TO HAVE THE LOCAL AND REGIONAL AS WELL AS THE NATIONAL PRESENCE TO HELP ENGAGE THE WORK THAT GETS DONE OVER THE PANDEMIC. THERE'S BEEN A PREMIUM ON ENGAGEMENT AND EXISTING CTSA PARTNERSHIPS AND COLLABORATIONS HAVE ENABLED THE COMMUNITIES DISPROPORTIONATELY AFFECTED TO HAVE AWARENESS OF THE ACTIVES AND TO BE MORE INVOLVED. WE NEED TO THINK WITH THE STRENGTHS EXEMPLIFIED BY THE LEADERSHIP THE CTSA BRINGS CLINICAL TRIAL CAPTURE AND DATA SHARING AND ADHERENCE AND HARMONIZATION AND ANALYSIS. THESE WERE ALL IMPORTANT FEATURES AS WE'VE MOVED FORWARD. IN COORDINATING THESE EFFORTS HAVE BEEN LED BY A VARIETY OF CTSA GROUPS THINKING ABOUT IDENTIFICATION AND SELECTION AND MANAGING THE COMPETING TRIALS AND DOING META-ANALYSIS AND SO FORTH. THESE ARE A VARIETY OF LESSONS LEARNED AND I WANTED TO GIVE A SENSE OF THE OVER ARCHING ONES. THE CTSAs HAVE BEEN INVOLVED AND TOMORROW WE'LL HEAR ABOUT WAYS WE'RE ENHANCING THE PROGRAM AND THIS IS A PLUG FOR TOMORROW'S PROGRAM TALKING ABOUT THE DIFFERENT CONSIDERATIONS AND WHAT WE'RE THINKING ABOUT FOR THE CONCEPTS SO STAY TUNED FOR THAT. I WANT TO END ON A FEW OTHER AREAS WE FOCUSSED ON. EPI MEANS ON TOP OF SO I THINK I MADE UP THE WORD EPI PANDEMIC AND THE WORK WE'VE DONE OVER COVID IN THE LAST COUPLE MONTHS. WE REFRESHED A TRAINING COURSE ON PRINCIPLES OF SCIENCE AROUND HOW THE PRINCIPLES HAVE BEEN OPERATIONALIZED IN A REAL WORLD PROJECT SETTING. SPECIFICALLY WE'RE DISCUSSING THE DEVELOPMENT OF A DRUG TO TREATMENT AND USE IT AS A MEANS TO GO THROUGH THE TRANSLATIONAL SCIENCE PROCESS. IT WAS A BIG SUCCESS LAST YEAR SO WE DID IT AGAIN THIS YEAR AND IT CAME FROM OUR EDUCATIONAL BRANCH WITHIN NCATS. WE'VE BEEN ACTIVE IN THE HEAL PROGRAM HELPING END ADDITION LONG-TERM AND APPLYING NEW DRUG DEVELOPMENT STRATEGIES FOR OPIOID MISUSE AND ADDICTION FOR PAIN. WE CURRENTLY HAVE 51 PROJECTS ONGOING AND SEVERAL DREW DIFFERENT PHASES. MOST CONDITIONS THE BREAK DOWN ON THE PIE CHART OF THE COMMISSION OF PAIN AND OPIOID DISORDER AND CONDITIONS OVERLAPPING. IN THE MIDDLE PIE CHART ARE THE P.I.s AND COLLABORATORS AND SECTORS OF THE COMMITTEE THEY COME FROM AND LISTING PROJECTS AROUND THE PLATFORM APPROACHES WE'VE BEEN USING AND WHAT I'VE TALKED ABOUT BEFORE. SO THAT GIVES A SENSE OF THE HEAL PROGRAM. AND THE LAST PROGRAM I'LL MENTION IS ONE THAT IS ADDRESSING STRUCTURAL RACISM WITHIN THE NIH AND SCIENTIFIC COMMUNITY. THIS PROGRAM IS CALLED UNITE. IT ADDRESSES FIVE MAJOR AREAS. NCATS HAS A PRESENTATION ON ALL THESE AREAS AND WITHIN THE COMMUNITY AND WE LOOK FORWARD TO SUPPORTING THIS UNITED EFFORT. HERE YOU STAND FOR UNDERSTANDING STAKEHOLDER EXPERIENCES THROUGH LISTENING AND LEARNING. UNITE STANDS FOR -- N STANDS FOR NEW RESEARCH ON HEALTH DISPARITIES, MINORITY HEALTH AND HEALTH EQUITY. I IS IMPROVING THE STRUCTURE FOR INCLUSION AND EXCELLENCE AND T IS FOR TRANSLATABILITY AND E IS THE EXTRAMURAL RESEARCH ECO SYSTEM TO PROMOTE WORKFORCE DIVERSITY. WE'RE EXCITED TO BE A PART OF THE PROGRAM AND TO LEARN OVER THE COURSE OF THE PERIOD AS THEY CONVENE AN PROVIDE RECOMMENDATIONS TO MOVE FORWARD AND HOW WE THINK ABOUT OUR INITIATES AND THE WORK WE SUPPORT FROM THE NIH PERSPECTIVE. SO HAPPY TO BE A PART OF THIS. I SHOULD ALSO SAY NCATS AND THE CTSA PROGRAM ARE EMBARKING ON OUR OWN EFFORT THROUGH THE STEERING COMMITTEE. AT THE CTSA PROGRAM STEERING COMMITTEE MEETING OR PROGRAM MEETING LAST YEAR THE FOCUS OF THAT MEETING WAS ON DIVERSITY, EQUITY AND INCLUSION. AND THERE WAS A STRONG CALL TO ACTION TO HAVE A CONSORTIUM FOCUSSED ON THESE EFFORTS THROUGH THESE DEI EFFORTS. THE STEERING COMMITTEE ESTABLISHED A TASK FORCE OF EXPERTS TO HELP DEVELOP A VISION AND IMPLEMENTABLE SOLUTIONS FOR THE PROGRAM SO STAY TUNED FOR THIS AND I LOOK FORWARD TO HEARING FROM THE DEI TASK FORCE ON THESE NEXT STEPS ANOTHER THING WE'RE EXCITED ABOUT IS WE'LL HAVE A 10th ANNIVERSARY AND WE'LL BE SENDING MORE DETAILS TO COME WE'LL THINK OF HOW NCATS' APPROACH IS BRINGING MORE TO MORE PEOPLE QUICKLY. SO WE'RE EXCITED ABOUT OUR 10-YEAR-OLD BIRTHDAY. IT'S EXCITING TO HAVE THIS MILESTONE SO STAY TUNED. NOW YOU KNOW THE NCATS WAY. WE'RE A SMALL BUT MIGHTY CENTER AT THE NIH AND IT'S GREAT TO SEE THE PRESIDENT'S REQUEST WITH AN INCREASE FOR FY22. WE'VE HAD STEADY GROWTH OVER THE YEAR AND IN FY21 WE HAD $855 AND FY22 WITH A 2.79% INCREASE PROPOSED AND YOU SEE THE TRENDS ON THE RIGHT. WE CAN ALSO DO A BREAKDOWN OF HOW THESE FUNDS ARE ALLOCATED ACROSS NCATS TO GIVE A SENSE OF WHAT THE PIE CHART LOOKS LIKE. LARGELY OUR CLINICAL PROGRAMS WITH CTSAs AND THE OTHER ARE BROKEN OUT OVER THE OTHER INITIATIVES THAT I'VE MENTIONED TODAY. YOU CAN SEE MORE DETAILS ON THIS SLIDE SHOWN HERE IF YOU'RE INTERESTED. THIS SHOWS THE LINK TO THE DETAILED PRESIDENTIAL PROPOSED. OVERALL THE NIH REQUEST IS $51 MILLION. A $9 BILLION INCREASE OVER LAST YEAR AND $6.5 BILLION IS BEING PROPOSED FOR A NEW PROGRAM CALLED ARPA-H AND I'LL GET TO THAT IN A SECOND. AND THEN THE NCATS PREDICT HERE AT THE TOP OF THE TABLE. THIS IS OUR BASE BUDGET WE WE'VE ALSO RECEIVED ADDITIONAL SUPPORT FOR THE PROGRAMS I MENTIONED PREVIOUSLY PARTICULARLY AROUND HEAL AND COVID. WE'VE HAD COLLABORATIONS WITH A LOT OF THE WORK GOING ON IN THE SPACE AND SO I'VE RESOURCED SOME OF THE SUPPLEMENTAL FUNDING TO SUPPORT THOSE ACTIVES. -- ACTIVITIES. I MENTIONED ARPA-H. THIS IS THE ADVANCED RESEARCH PROJECTS AGENCY FOR HEALTH. THIS IS ALSO AT THE PRESIDENT'S PROPOSED BUDGET. AND THIS IS WHEN WE KNOW AT THIS POINT. ESSENTIALLY ACCORDING TO SOME OF THE RELATED DOCUMENTS OUT THERE, THE IDEA IS ARPA-H WILL DRIVE TRANSFORMATIONAL RESEARCH AND DRIVE HEALTH BREAKS THROUGH AND HAVE A DISTINCT CULTURE AND ORGANIZATIONAL STRUCTURE AND COMPLIMENT THE NIH AS A DISTINCT PORTFOLIO. DR. COLLINS HAS ANSWERED PRELIMINARY QUESTIONS ABOUT ARPA-H AT THE NIH CONGRESSIONAL TESTIMONIES LAST MONTH AND STILL IN DISCUSSIONS WITH THE INSTITUTES AND CENTERS. THOSE ARE JUST STARTING. TOMORROW THERE'LL BE A PRESENTATION ON ARPA-H IF YOU'RE INTERESTED. I'M GOING TO STOP THERE AND HOPE WE CAN END AND HAVE TIME FOR QUESTIONS. I'M GOING TO OPEN IT UP NOW AND TAKE IT AWAY. >> HI, JOANIE. THIS IS CLAIRE. CAN YOU HEAR ME? >> YES. >> WE HAVE A COUPLE OF QUESTIONS AND A COMMENT FROM DR. VANDENBERG. THE FIRST QUESTION REFERS BACK TO THE CHART YOU HAD ABOUT THE NUMBER OF THERAPEUTICS AND PREDICTIVE MODEL AND WONDER YOU NEED TO MAKE THE DATE AN ACCOUNTABLE GOAL? >> IT IS ASPIRATIONAL AT THIS POINT. WE DON'T HAVE HARD AND FAST DATA TO SAY THAT'S A HARD AND FAST NUMBER. THAT'S WHY IT'S A LITTLE -- THE IDEA WAS TO JUST DESCRIBE THE FACT THAT IF WE'RE SUCCESSFUL IN THE PILOTS WE'RE DOING RIGHT NOW, WE THINK THE NUMBER IS ASPIRATIONAL AND WE ALSO THINK IF THOSE GO WELL AND CAN MAKE THE IMPROVEMENTS WE EXPECT AND GET THEM THROUGH CLINICAL TRIALS WE EXPECT THEM TO HAVE A MORE REAL NUMBER UNDERNEATH THEM AND THEN WE'D BE ABLE TO EXTRAPOLATE ON A MORE CONFIDENT BASIS WHAT THE NUMBER MAY LOOK LIKE. >> OKAY. >> AND THE SECOND QUESTION WAS THE NCATS MANDATE INCLUDE GIVING THERAPEUTICS TO PEOPLE, ALL PEOPLE OR STOP AT FDA APPROVAL. >> THE QUESTION IS WHETHER YOU HAVE OWNERSHIP TO GET THERAPEUTICS TO CLINICAL PRACTICE. THINK OF THE THERAPEUTICS FOR RARE DISEASES THAT MEANS CLINICAL PRACTICE HAS TO BE ABLE TO IDENTIFY THOSE PEOPLE WITH THAT DISEASE AND ASSURE THE RIGHT THERAPEUTIC IS GIVEN TO THE RIGHT PERSON AT THE RIGHT TIME IN THE STAGE OF THE DISEASE. I'M CURIOUS WHETHER NCATS' MISSION INCLUDES FOLLOWING NEW THERAPEUTICS THAT ARE DEVELOPED WITH ITS TOOLS ALL THE WAY THROUGH THE PROCESS TO CLINICAL PRACTICE. >> THANKS FOR EXTENDING ON THAT, GEORGE. GREAT QUESTION. THE IDEA IS FOR SURE THAT WE SPAN THE ENTIRE CLINICAL TRANSLATIONAL SPECTRUM. THAT INCLUDES PHASE 4 AND PUBLIC HEALTH. THOSE ARE IN OUR PURVIEW. ESPECIALLY AS WE THINK ABOUT DISSEMINATION AND DISSEMINATION AND IMPLEMENTATION IS A SKI GOAL FOR US -- A KEY GOAL FOR US AND SOMETHING WE'RE INTERESTED IN WORKING ON AND IMPROVING AS WE THINK ABOUT THESE PARTICULAR AREAS MOVING FORWARD BECAUSE AS YOU POINTED OUT RARE DISEASE RARE AND DEVELOPING THE TOOL KIT FOR PATIENTS TO FIND PHYSICIANS AND MORE ABOUT THAT IF THEY GET DIAGNOSED AND FINDING RIGHT MEDICATIONS AND MAKING SURE WE INFORM THE PHYSICIANS THEMSELVES OF NEW TREATMENT OPPORTUNITIES AVAILABLE FOR THOSE SORTS OF RARE DISEASES. IT'S ALL ACROSS THE SPECTRUM, ACTUALLY. THANK YOU. >> TO WRAP UP, GEORGE, THERE WAS A COMMENT. WE DIDN'T SEE MUCH REFERENCE TO INDUSTRY INTERACTION. WE WORK WITH INDUSTRY AND ABOUT EVERYTHING WE DID WITH COVID-19 WAS A PUBLIC-PRIVATE PARTNERSHIP WITH INDUSTRY AND ACADEMIA AND THE FEDERAL GOVERNMENT. VERY MUCH SO REPRESENTS THE SPACE AND WHAT WE DO IS MOVING ACROSS THE SPACE AND FROM WHAT WE DO TO THE INDUSTRY AND VICE VERSA. IT'S AN ECO SYSTEM. MAYBE THAT'S HOW I SHOULD REFER TO IT. >> WHEN YOU TALK ABOUT SAEASSAYS AND PUTTING INFORMATION OUT THERE I'M GUESSING NOTHING WAS A SUPER HIT IN ANY PARTICULAR SITUATION WHERE WE HAD A PREEXISTING DRUG TO BE USED AS A THERAPEUTIC. >> THEY'RE STILL BEING EVALUATED BUT ONE EXAMPLE OFF THE TOP OF MY HEAD AND I WON'T REMEMBER THE DRUG, SORRY ABOUT THAT. EARLY ON WHEN HYDROXYCHLOROQUINE HAD SOME FAVOR IN THE TREATMENT SPACE FOR COVID-19, WE WERE LOOKING AT THE THERAPEUTICS AND WE TOOK THESE COMPOUNDS AND TESTED THEM ON TISSUE CHIPS THAT REPRESENTED THE LUNG. SOME WORKED BETTER AND THESE ARE CONTINUING TO BE EVALUATED GOING FORWARD. >> I HAD A QUESTION ON THE COURSE YOU TALKED ABOUT ON YOUR SLIDES DEVELOPED ONLINE COURSE. IS THAT COURSE PUBLICLY AVAILABLE? CAN ANYONE DOWNLOAD THE MATERIAL OR IS IT IN PRINCIPLE ONLY BY REGISTRATION? YOU PLAN TO RUN IT WITH FACULTY? CAN YOU TALK ABOUT IT? THE REASON I ASK TO GIVE CONTEXT IS WHEN I WAS AT THE NIH I HELPED DEVELOP THE TRANSLATIONAL SCIENCE COURSE THAT CHRIS AND I USED TO TEACH AND CONTINUE TO DO AND IN FACT IN JULY I'LL BE COMING BACK TO TEACH THAT ONE AGAIN. I WANT TO UNDERSTAND WHAT THE MATERIAL WAS YOU COVERED BECAUSE OBVIOUSLY WE TEACH THE PSTP COURSE WITH DEEP INVOLVEMENT WITH NCATS AS FACULTY AND THE INTERNET PROGRAM ASIDE OF THE PRESENTATION AND ALL THAT SO WANT TO BETTER UNDERSTAND >> AND THE TRUTH IS I ACTUALLY DON'T KNOW HOW YOU GET ACCEPT TO IT BUT IT'S THROUGH THE FAES COURSE AND I'LL ASK AND SEND YOU THE INFORMATION I FIND OUT ABOUT GETTING ACCESS TO THAT COURSE. IF YOU HAVE TO REGISTER I'LL LET YOU KNOW BUT WE CAN FIGURE THAT OUT AND A CAN GIVE YOU THE ANSWER. >> THANK YOU. PRESUMABLY ARPA-H IS A TAKE ON DARPA THE HEALTH VERSION OF DARPA. WE CHOSE NOT TO CALL IT HARPA AND YOU'RE CALL IT ARPA-H IS THAT IT? >> THAT'S WHAT I HEARD TOO IT'S KIND OF BUILD AROUND THINKING WHAT DARPA IS AND DOES AND MOVING THAT IN THE HEALTH AND NIH HAS THOSE AND CONTRACTS AND GRANTS AND THE MECHANISMS WE'RE FAMILIAR WITH ARE USED AS WELL. THE IDEA IS TO BE BUILT LIKE WHAT THAT IS TO HAVE EXPANDED AUTHORITIES AROUND THE USE OF THESE TYPES OF MECHANISMS IN THE HEALTH SPACE. SO I DON'T KNOW HOW THEY CAME TO THE NAME OF ARPA-H VERSUS ARPA H. >> THE UNDERLYING THEME AND IN FAIRNESS MAYBE I HAVE AN ADVANTAGE HAVING SIGNIFICANT ANALYSIS ON THE NIH PORTFOLIO IN MY EARLY DAYS AND THE OTHER AUTHORITY OTHER THAN THE NCI FREDERICK CENTER AND A LITTLE BIT OF THAT IN THE CONTEXT OF NCATS IS NOT REGULARLY USED BY THE IDEA OF THE AUTHORITY AS A BRANCH IN THE NIH IS EXTREMELY ATTRACTIVE TO MOVE FASTER. SO THE QUESTION I HAVE FOR YOU IS IF ARPA-H IS SET UP TO DO THIS, WHAT HAPPENS -- HOW DID NCATS FIT INTO THAT? IN A SENSE YOU CAN ALMOST SEE ARPA-H HAVING A FAIRLY OVERLAPPING MISSION WITH WHAT NCATS IS TRYING TO DO. >> I THINK THAT'S A REASONABLE ANALYSIS. AGAIN, THE MAIN THING IS WE REALLY DON'T KNOW AT THIS STAGE WHAT'S GOING TO HAPPEN BUT WHEN YOU AND MAYBE WE'LL FIND OUT A LITTLE BIT MORE TOMORROW AS WELL BUT THE TRUTH IS THESE ARE DISCUSSIONS JUST NOW STARTING SINCE THE PRESIDENT'S BUDGET WAS RELEASED. THIS WILL START TO UNFOLD AND WE'LL TALK ABOUT IT MORE AND WOULD SAY AND I CAN -- WHEN WE'RE TALKING ABOUT GETTING MORE TREATMENTS AND THAT'S SOMETHING IN MY MIND AND MY GOAL IS TO THINK ABOUT WAYS IN WHICH WE CAN POSITION OUR SELVES TO HELP THAT AS MUCH AS POSSIBLE. >> OKAY, THANK YOU. >> IF I CAN INTERACT, JOANIE -- INTERJECT, THERE'S A FEW OTHER QUESTIONS RELATED TO ARPA-H AND I'LL READ THEM QUICKLY. AGAIN, WE DON'T KNOW MUCH SO YOU MAY NOT BE ABLE TO GIVE MUCH MORE OF AN ANSWER. ONE IS HOW DO YOU THINK ARPA-H AND NCATS INITIATIVES WILL INTERACT GOING FORWARD. AND COLLINS TESTIFIED ARPA-H IS NCATS ON STEROID SO MIGHT IT BECOME PART OF ARPA-H? THERE'S CONCERNS NCATS HAS BEEN A HUGE CHAMPION FOR RARE DISEASE WHEREAS THE ARPA-H FOCUS IS NOT IN THAT AREA SO HOW WILL WE ENSURE RARE DISEASE RESEARCH AND TRANSLATION CONTINUES TO BE A PRIORITY. SO IF YOU WANT TO JUST -- WAIT, THERE'S ONE MORE AT THE BOTTOM ABOUT A POTENTIAL COMPETITIVE OVERLAPPING MISSION OF ARPA-H. SO IF YOU CAN ADDRESS ANY OF THAT, THAT'D BE GREAT. >> OKAY. SO IN TERMS OF ARPA-H AND THE INITIATIVE NCATS WOULD DO, THIS SAY GREAT QUESTION. AT THIS POINT WE STILL DON'T KNOW FIRST OF ALL WHAT WILL HAPPEN WITH ARPA-H AND WHERE IT WILL END UP WILL IT END UP IN THE NIH IF IT COMES INSIDE THE NIH WHERE WOULD IT BE. THESE ARE ALL QUESTIONS WE STILL DON'T HAVE A GOOD HANDLE ON. AND SO AS IT RELATES TO SOME OF THE INITIATIVE WE DO, I THINK NCATS WOULD BE IN A GOOD POSITION TO COORDINATE OR COLLABORATE WITH MANY OF THEM. CERTAINLY THAT WOULD BE ONE OF THE GOALS IF AND WHEN THAT HAPPENED NO MATTER WHERE IT WAS. SO REALLY MORE TO BE SEEN HERE. I THINK AS THE CONVERSATIONS START TO UNFOLD, WE'LL HAVE MORE CLARITY MOVING FORWARD SIMILARLY WITH THE CTSAs IT'S SAME WITH RARE DISEASES. AND WE'RE 6: -- PASSIONATE ABOUT RARE DISEASES AND THINK IT WILL FRONT AND CENTER ROLE AND WANT TO BE POSITIONED WELL TO INTERACT WITH ARPA-H AND WHATEVER SHAPE OR FORM IT TURNS INTO. >> OKAY. LET ME MOVE ON. PAUL HARRIS ASKED IF YOU CAN GO BACK A FEW SLIDES AND SO JOANIE CAN GIVE MORE DETAIL ON THE ADD-/NO ADD LANGUAGE FOR NIH BUDGET ITEMS. >> THE ADD/NON-ADD. WHAT'S THAT MEAN? >> WE BROKE OUT THE CTSA PROGRAM AND THE CAN PROGRAM BECAUSE THEY'RE DIFFERENT. ONE'S A LINE ITEM AND ONE IS SPECIAL AUTHORITY FOR NCATS AND THE TOTAL NCATS APPROPRIATIONS REPRESENTS MORE THAN WHAT'S JUST SHOWN THERE. THE ITALICIZED LINES ARE THERE. HOPE THAT ANSWERS YOUR QUESTION. >> THANK YOU, JOANIE. >> THAT WAS CONFUSING. I DEBATED TO SHOW IT THAT WAY AND DIDN'T EXPLAIN WELL SO THANK YOU FOR ASKING. >> ARE SIMILAR EFFORTS ADMITTEDLY LESS AMBITIOUS THE FDA OFTEN ENDS UP NOT ON THE SAME PAGE. HOW DO WE PRE SET THIS SO THEY ARE? >> I WATCHED A LOT OF SHIPS >> MARSHALL, THANKS FOR THAT QUESTION. WE LEARNED EARLY ON ENGAGING THE FDA BEFORE WE EVEN ARE THINKING ABOUT -- OKAY, SO WE THOUGHT ABOUT IT BUT IF YOU'LL EXCUSE THE TURN OF PHRASE, BEFORE IT'S EVEN A GLIMMER IN OUR EYE, WE'RE THINKING ABOUT WHAT NEEDS TO BE DONE WITH THE FDA NOT NECESSARILY WHAT NEEDS TO BE DONE BUT HOW WE NEED TO ENGAGE THEM AND WHO IT IS WE NEED TO ENGAGE AND FOR A WHILE THE PROGRAMS I MENTIONED TODAY THESE 3-D MODELS MEANT TO BE PREDICTIVE FOR TOXICITY AND EFFICACY, WE'LL ONLY LEARN THAT IF WE WORK HAND IN HAND WITH THE FDA. THE TISSUE CHIP PROGRAM WE HAVE AND THE FDA HAS A LAB WITHIN THE FDA TO USE TISSUE CHIPS AND TO DO THEIR OWN STUDIES AGAIN TO MAKE SURE WE'RE UNDERSTANDING WHAT THE REGULATORY HURDLES ARE GOING THROUGH THE SCIENCE BEING CONDUCTED SO WE CAN IDENTIFY THOSE OPERATIONAL CHALLENGES OR THE SCIENTIFIC CHALLENGES TOGETHER AND WORK ON WAYS TO ADDRESS THEM. THE OTHER THING I WOULD SAY IS WE WERE CONNECTED WITH THE REGULATORY SCIENCE COMMUNITY AS WELL AND HELPED DEVELOP SOME AGENDAS FOR THE REGULATORY SCIENCE MEETINGS ONE HAPPENED LAST SEPTEMBER VIRTUALLY AND THESE ARE ALSO PLACES WHERE WE'RE ABLE TO REALLY CONNECT WITH THE FDA, TALK ABOUT SOME OF THE RECENT FINDINGS WE HAVE AND WHAT IMPLICATIONS THOSE MIGHT HAVE FOR THE REGULATORY SCIENCE AND WE REALLY THINK OF THE FDA AS PARTNERS HERE AND THE WORK WE'RE DOING AND FOR THE GENE THERAPY WORK I MENTIONED AS WELL. WE'RE WORKING WITH THEM SPECIFICALLY PETER MARKS TO HELP US GO THROUGH THAT PROGRAM TOGETHER. >> CAN I ASK A FOLLOW-ON. IT'S MORE OF A SPECIAL QUESTION. IS THERE ANY WAY WHERE ONCE IT'S BEEN APPROVED FOR FUNDING BY HIN BEFORE IT ACTIVATES IF IT'S GOING TO BE SOMETHING THAT WOULD EVENTUALLY INVOLVE THE FDA? IS THERE A WAY TO HAVE THEM DO A REVIEW BEFORE THE STUDY'S DONE SAYING YES, WITH THIS MINOR TWEAK, THIS WILL BENEFIT WITH WHAT KIND OF INFORMATION WE NEED TO ACCEPT THIS LATER ON NOT FOR A DRUG APPROVAL BUT FOR THE TYPE OF DATA THEY WOULD THEN ALLOW IN. IS THERE A WAY TO FORMALIZE THAT SO IT ACTUALLY HAS SOME BITE OR MEETING? -- MEANING. >> IT SOUNDS REASONABLE IN SETTING UP A PROCESS LIKE THAT. IT'S SOMETHING WE CAN LOOK INTO AND AS IT A GREAT IDEA, MARSHALL AND HAVE TO THINK OF THE WHEN AND HOW AND TIMING AND ALL OF THAT AND WHAT THE REVIEW WOULD BE. THERE'S A BIT OF AN INFRASTRUCTURE BUT THINKING ABOUT IT NOW IS BRILLIANT. I LIKE THIS IDEA AND WE CAN START THINKING HOW IT MIGHT BE IMPLEMENTED. >> IT COMES WITH CONVERSATIONS I'VE HAD WITH JANET AND I THINK SHE'D BE VERY OPEN TO THIS AND WORK OUT IN. >> HAPPY IT HELP. >> WE HAVE A QUESTION FROM ANDY KENNEDY. SHE SAYS THANKS FOR THE FANTASTIC OVERVIEW. CAN YOU TALK ABOUT FORMALIZED MECHANISM FOR COLLABORATING WITH OTHER AGENCY PARTNERS OUTSIDE OF OTHER NIH I.C.s. AND INDUSTRY PARTNERS WITHIN THESE EFFORTS. >> WE AN NCATS FELLOWSHIP BRINGING IN STUDENTS TO THE FDA FOR A PERIOD OF TIME AND COME BACK TO NCATS FOR FELLOWSHIP. LOOKING FORWARD TO THAT FELLOWSHIP. EXACTLY THESE SORTS OF REASONS TO THINK OF HOW TO STREAMLINE THE COLLABORATIONS AND ULTIMATELY THE PROJECTS WE WANT TO ADVANCE AND MOVE FORWARD. SO THAT'S ONE EXAMPLE. YOU MENTIONED THE CTSAs. THERE'S A VARIETY OF WAYS IN WHICH TO WORK WITH EXTERNAL STAKEHOLDERS AS WE THINK OF THE WORKSHOPS AND THE CONVENINGS WE HAVE. WE OFTEN INVITE PEOPLE WHO REPRESENT THOSE COMMUNITIES TO COME TO THE MEETING. THERE'S A MEETING AT THE SAME TIME UNFORTUNATELY I'M NOT ABLE TO ATTEND IT AND TALKING ABOUT GENE TARGETED THERAPIES. IT'S A THREE DAY MEETING OVER THE COURSE OF THREE WEEKS. SO ONE A WEEK OVER THE LAST THREE WEEKS. AND WE HAVE BROUGHT IN SOME PATIENT ADVOCACY REPRESENTATIVES TO BRING THE PATIENT PERSPECTIVE TO THE DISCUSSION. THOSE SORTS OF THINGS INCREDIBLY IMPORTANT FOR US TO UNDERSTAND AND HEAR FROM THE PATIENT COMMUNITY AND UNDERSTANDING WHAT THEY'RE THINKING ABOUT AND THEIR WORRIES ARE AND HEARING FROM PATIENTS AND UNDERSTANDING THE SENSE OF URGENCY TO SEE WHAT NEEDS TO HAPPEN TO MOVE FORWARD. THE SHORT ANSWER IS YES. WE WORK WITH GROUPS ACROSS THE STAKEHOLDER ENVIRONMENTS TO BRING TO THE TABLE AS WE THINK ABOUT THESE CROSS-CUTTING COLLABORATIONS AND PARTNERSHIPS AND WORKING GROUPS WE PULL TOGETHER AS A CONVENING FUNCTION OF SOME THINGS WE DO. >> THIS IS ANNIE. CAN I ADD A FOLLOW-UP QUESTION. YOU GUYS ARE CERTAINLY LEADERS IN THE SPACE OF CONVENING AND COLLABORATING IN THE EARLY DIAGNOSTIC WORKSHOP AND THIS IS AN UNFORTUNATE OVERLAP OF MEETINGS TODAY. IT'S BEEN A FANTASTIC MEETING AND WHAT MADE ME THINK OF IT IS THE COVID WORK YOU'VE BEEN TALKING ABOUT AND SIMILAR LEADERSHIPS BEING UNDERTAKEN BY EXAMPLE CDC. ARE THERE EFFORTS TO PULL IN SURVEILLANCE. THERE'S GREAT WORK AND LOOKING AT OTHER CONVENERS DOING SIMILAR WORK SO WE DON'T HAVE DUPLICATIVE EFFORTS. >> I COULDN'T AGREE MORE. THE SHORT ANSWER IS YES BUT ESSENTIALLY OVER THE COURSE OF THE COVID PANDEMIC AND THE OPEN DATA PORTAL I SHOWED WITH THE VARIANT DATA FROM THAT, THOSE ARE ALL -- THAT'S ALL WORK WE PROVIDE FOR THE CDC AS WELL AS THEY THINK ABOUT THEIR PUBLIC HEALTH IMPLICATIONS OF THAT. IT'S ONE OF MANY RESOURCES THAT THEY USE BUT THAT IS AMONG THEM. AND THERE'S A GROUP ACROSS THE FEDERAL AGENCIES TALKING ABOUT THESE TYPES OF SYSTEMS AND LEVERAGING THEM TOGETHER WHERE WE CAN BRING OUR STRENGTHS TO THE TABLE. THAT'S ONE EXAMPLE AND I TALKED ABOUT ONE OF THE THINGS WE'RE TRYING TO DO IS HAVE THE ELECTRONIC HEALTH RECORDS FROM THE PARTNERS BUT UNDERSTANDING FOR EXAMPLE THE DEPTH DATA INDEX TO UNDERSTAND HOW IT MIGHT IMPACT THE ARTIFICIAL INTELLIGENCE DATA MODELS WE USE. THOSE TYPES OF DATA WOULD BE IMPORTANT TO GET AT. SO WE'RE WORKING RIGHT NOW WITH THE CDC IN WAYS TO GET ACCESS TO THOSE DATA AND BRING THOSE INTO THE DATABASE IN SOME WAY, SHAPE OR FORM AND WE'RE LOOKING AT WAYS TO MANAGE THAT. AS THE A GREAT QUESTION AND I COULDN'T AGREE MORE. >> THANK YOU. >> OKAY. I WANTED TO LET YOU KNOW IF YOU LOOK IN THE CHAT BOX THERE'S LINK FOR THE TRAINING COURSE. >> THANK YOU. THERE'S A HAND UP AND GEORGE DID YOU STILL HAVE A QUESTION? >> I HAVE A COUPLE COMMENTS ON THE THINGS BEING DISCUSSED. FIRST ON ARPA-H ONE OF THE CONCERNS WE HAD HERE IN DOWNTOWN D.C. CONGRESSIONAL EXPERTS TELL ME THAT WAS THE PRODUCT OF LOBBYING INSIDE THE PANCREATIC CANCER COMMUNITY. AS WE KNOW FROM PRESIDENT BIDEN'S ADDRESS TO CONGRESS THE THREE AREAS WE'RE FOCUSSED ON ARE CANCER, ALZHEIMER'S AND DIABETES WHICH ARE ALL WELL FUNDED AND PRIORITIZED. RARE DISEASE REMAINS CHRONICALLY UNDER FUNDED AND A CONCE -- WE HAVE TO LOOK AT HOW TO HELP THE MOST PEOPLE AND A RISING TIDE LIFTS ALL BOATS. SEPARATE FROM THAT I WANT TO SAY THE COLLABORATION IS IMPORTANT AND PAVE THE WAY FOR ONCE THE APPROVAL COMES THROUGH OUR PATIENTS STILL HAVE EXTREME DIFFICULTY ACCESSING TREATMENTS AND THERAPIES. I THINK IT'S AND WE'RE FINDING PAYERS WILL NOT COVER TREATMENTS IF THEY DON'T SEE THE VALUE IN THEM. AND FINALLY, ONE EXAMPLE WE'VE BEEN SEEING RECENTLY AND I'VE SEEN THIS THEY'RE SAYING THE ECONOMIC COST OF GENOMIC SEQUENCING FOR A WHOLE GENOME AND EXOME IS A FEW HUNDRED DOLLARS IT SEEMS AFFORDABLE. WHAT WE'RE SEEING IN PRACTICE IS THE COST TO THE CONSUMER S COULD BE $500,000 TO $20,000. THERE'S THE ECONOMIC COSTS AND THE ACTUAL COSTS BEING PRESENTED TO PATIENTS AND PAYERS. I THINK IT'S IMPORTANT TO GET MESSAGE OUT BECAUSE ON THE HILL RIGHT NOW THERE'S TWO HILLS BEING DEBATED. PETERS AND SWALWELL WERE TRYING TO GET A COMPROMISE TO HAVE MEDICAID COVERAGE FOR GENOMIC SEQUENCING AND ONE OF THE AREAS THAT NEEDS TO BE CLARIFIED IS AS THE NOT A FEW HUNDRED DOLLARS FOR A TEST IN PRACTICE. NIH CAN BE INSTRUMENTAL IN LAYING THE GROUND WORK TO OPERATE ACROSS THE DIVISIONS TO MAKE SURE AT THE END OF THE DAY YOU HAVE THE BENCH TO BEDSIDE. >> THESE ARE THINGS TO THINK ABOUT IN THE FUTURE. WE HAVE A ROLE TO PLAY AND IT'S ABOUT THE SCIENCE AND ABOUT THE OPERATIONAL ADMINISTRATIVE FINANCIAL AND OTHER BARRIERS. IF WE CAN FIGURE OUT WAYS TO BRING THE COMMUNITIES IN FOR THIS TYPE OF DISCOURSE WE CAN UNDERSTAND WHAT'S NEEDED TO HELP INFORM THESE SORTS OF THINGS BEING DECIDED UPON THAT'S SOMETHING WE CAN CONTRIBUTE IN BETTER WAYS TO THE ECO SYSTEM WE HAVE. THANK YOU FOR YOUR COMMENTS. >> JOANIE, YOU MAY WANT TO MENTION THE NCATS FDA FELLOWSHIP. NOT SURE IF THAT WAS WIN UN THE SLIDES -- IN ONE OF THE SLIDES. WE HAVE A FIRST BATCH OF STUDENTS COMING AND A THEY'LL SPEND TIME AT THE FDA AND THE NCATS LABS AND EXCITE ABOUT THE NEW FELLOWSHIP AND HOPE TO TELL YOU MORE AS WE GAIN EXPERIENCE. >> I'LL DO TWO MORE FROM THE CHAT AND MARSHALL AND THEN WE'LL HAVE TO GET ON TO OUR NEXT SPEAKER. SO DR. JACKSON, COULD YOU PLEASE EXPAND ON WAYS THAT NCATS MIGHT ENVISION OR CATALYZE THE INNOVATIONS AND STRENGTHS ARISE FROM THE CENTERS OF PRE CLINICAL TRANSLATION AND ACCELERATE TRANSLATION OF NEW TREATMENTS FOR IMPROVED HEALTH. THE QUESTION IS WHERE ARE THE OPPORTUNITIES OF HOW THOSE COULD WORK ON COMBINED PROJECTS OR IDEAS OR INNOVATIONS OR ROAD BLOCKS. THAT COULD MAKE THE NEXT BIG TRANSFORMATIVELY. >> THE INTERNAL THEME OR D.P.I. HAS ENABLED 44 INVESTIGATION NEW DRUGS OR IMD APPLICATIONS S THEY HAVE RECEIVED THE LETTER FROM THE F.D.A. TO ENABLEEL EVALUATION AND HUNDREDS OF PUBLICATIONS AND DISCOVERIES. A LOT OF WEB BASED ACCOMPLISH-FACING INSEM NATURE, SOFTWARE, DATASETS, MANY OTHER PRODUCTS. AMOUNT OF THESE PRODUCTS ARE NOT EASILY DISSEMINATED OR NOT EFFICIENTLY DISSEMINATED TO PEER REVIEW PUBLICATIONS REALLY SO WE NEED TO WORK AND WE HAVE WORKED ON DEVELOP PUBLIC-FACING TO SPREAD THE WORK AND DISSEMINATE THESE PRODUCTS AND YOU WILL SEE EXAMPLES TO THIS AFFECT. LAST BUT NOT LEAST, WE MAY A LOT OF PRODUCTS PUBLICLY AVAILABLE ALMOST IMMEDIAT IMMEDIATELY. SOME FROM CASES WE PAT END AND DISSEMINATE AND LATE STAGE TO ACCESS TO LICENSING AND BEGAN AND WE'VE DONE A LOT OF WORK IN THAT SPACE AND YOU'VE BEEN VERY JUDICIOUS IN TERMS OF WHAT WE PATENT AND WHAT WE MADE PUBLICLY AVAILABLE WITHOUT PAT ANTING. SO, THE TAGLINE YOU HAVE SEEN IT ACTUALLY ON SLIDES AND WEB SITES, IS COLLABORATING INNOVATIVE ACCELERATE SO HOW ARE WE, IN THE LABS, AT D.P.I., PUTTING THIS INTO ACTION? TO ME, COLLABORATE AND INNOVATE ARE VERY MUCH RELATED TERMS. YOU COLLABORATE BECAUSE YOU ARE INNOVATING, YOU ARE INNOVATING WHILE YOU ARE COLLABORATING SO FOR THOSE TWO, I WANT TO GIVE YOU SEVERAL EXAMPLES AS TO HOW WE SUBSTANTIATE THIS. WE'RE ENGAGING A BROAD RANGE OF STAKEHOLDERS TO ADVANCE TRANSLATION. THIS IS NOT RANDOM, AGAIN, SIGNS IN THE AGENT STAKEHOLDERS. ENGAGING MULTIPLE DISCIPLINES AND AREAS OF EXPERTISE TO DRIVE INNOVATION, WE CANNOT SOLVE SOME OF THESE CONCEPTUAL PROBLEMS BY DOING IT JUST ON OUR OWN SO WE'RE BUILDING THESE NETWORKS TO ADVANCE TRANSLATION, TO SOLVE TRANSLATIONAL PROBLEMS BY REALLY BRINGING DIFFERENT DISCIPLINES TOGETHER. RESPONDING TO PUBLIC-HEALTH EMERGENCIES. THIS IS IMPORTANT BECAUSE SEW TEE TO RESPOND. WE'RE A FEDERAL LAB AFTER ALL THE AND WE ASK TURN ON AND RESPOND BY VARIOUS STAKEHOLDERS AND WE HAVE DONE SO SUCCESSFULLY. LAST BUT NOT LEAST, ACCELERATE. THIS IS REALLY THE AMPLIFIER WITH THE VIEW AND WE'RE ALL ABOUT DELIVERING OR FINDING SOME KNOW HOW TO OTHERS SO THEY CAN PRACTISE THE SAME THING AFTER WE DISCOVER, VALIDATE AND WE TRY TO DISSEMINATE THOSE AND OTHERS SO YOU WILL SEE EXAMPLES TO THIS EFFECT. SO, THE FIRST POINT, ENGAGING A BROAD RANGE AND EXPLANATION AND PATIENTS REALLY IN THE CENTRE OF THIS. EVEN THOUGH WE'RE A PRE CRITICAL UNIT OFEN CATS, WE DON'T HAVE A CLINICAL GROUP AND WE DON'T HAVE CLINICAL TRIALS OURSELVES AND WE THINK ABOUT PATIENTS ALL THE TIME SO, THREE CATEGORIES OF EXAMPLES HERE, AND I KNOW WE HAVE A GOOD AMOUNT OF TIME, WE'RE WORKING ON MANY PROJECTS ACROSS D.P.I. SO, MY EXAMPLES WILL BE LIMITED BY DEFAULT, BY NECESSITY, WORKING WITH PATIENTS, FAMILIES AND FOUNDATIONS AND WORKING WITH CLINICAL PROVIDERS TO ACTUALLY EFFECT THE TESTING FOR THE NEW THERAPEUTIC CANDIDATE AND I MENTIONED THIS EARLIER AND WORKING BACKWARDS, CROWDSOURCES TO BUILD NEW THERAPEUTIC HYPOTHESIS SO, THE FIRST EXAMPLE, OUT OF MANY, THIS IS WE'VE DONE A LOT OF WORK IN THE EARLY STAGES OF THERAPEUTIC DISCOVERY. ACROSS THE ORGANIZATION, AND GIVING YOU JUST ONE EXAMPLE TODAY, BEGAN FOR REASONS AT TIME, AND SO THIS IS WHERE WE ACTUALLY HAVE A NUMBER OF COLLABORATIONS WITH DISEASE FOUNDATIONS, PATIENT ADVOCACY GROUPS, SOMETIMES IT'S JUST ONE FAMILY IT STARTED IN THE FOUNDATION TO DEVELOP TEST MODELS FOR PRIMARILY INHERITED GENETIC PATIENTS. THE GOAL THERE IS TO CONDUCT EARLY STAGE DISCOVERIES AND CHARACTERIZATION AND CANDIDATE MOLECULES. IN A LOT OF CASES THEY USE THE FOUNDATION TO CROWDSOURCE THE FINDING WITH AN ACTUAL THERAPY OUTSIDE OFENCAT BUTTE BUT IT IS THE ENABLENINITIAL CATALYST. THIS IS A WIN-WIN-WIN BY EXAMPLE. THE OBJECTS ARE ACTUALLY CHAMPIONED BY POST DOCTORAL FELLOWS WORKING WITHIN THE LABS OR D.P.I. AND THERE ARE ALSO WORKING WITH THE FOUNDATION SCIENTIFIC ADVISORY BOARD RECEIVING SUPPORT FROM THE FOUNDATION. A LOT OF TIMES THESE PEOPLE HAVE ACTUALLY RECEIVED THEIR TRAINING IN A LAB THAT FOCUSES WITH A PARTICULAR DISEASE AND SO THE POST DOCK RECEIVES TRAINING OPPORTUNITIES AND TRANSLATION THAT IS AT THE LEVEL OF DRUG DISCOVERY EFFORTS SEEN IN MAJOR PHARMACEUTICAL ORGANIZATIONS SO THEY'RE READY FOR THEIR NEXT STEP IN TERMS OF THEIR CAREER PATH. THEY'RE ABLE TO DISSEMINATE THEIR FINDINGS TO PUBLICATION AND RELATED PLATFORMS. THEY GET THIS PERSONAL SATISFACTION OF BEING ABLE TO CONTRIBUTE A NEW THERAPY POTENTIALLY FOR THE PATIENTS. THEY'RE REALLY THE LAST BULLET, IS THE MOST IMPORTANT ONE. PATIENTS AND ADVOCATES ARE INTEGRAL TO THIS COLLABORATION PROCESS AND TO ITS SUCCESS. THE IMAGES BELOW ARE VARIOUS SNAP SHOPS FROM PATIENTS, FOUNDATION PEOPLE, VISITING OUR LABS AND SCIENTISTS LEARN WHOM THEY'RE WORKING ON BEHALF OF OR FOR AND THEY SEE THE PATIENTS MODERNIZATIONAL. THE PATIENTS INCURRED SEED THE ENVIRONMENT WHERE THEIR DISEASE IS STUDIED AND THERAPIES WERE DISCOVERED. WE'VE DONE THIS MANY TIMES OVER THE YEARS AND REALLY IT'S BEEN TRANSFORMATIONAL IN TERMS OF ALSO CHARTING THE PATH OF JUNE TRAINEES MOVING ON TO THEIR NEXT POSITIONS. JUVENILE MIO SIGHT IS, THIS IS AN AUTOIMMUNE DISEASE WITH MUSCLE WEAKNESS AND FATIGUE, PAIN. I'M NOT GOING TO GO THROUGH ALL THESE POINTS ON THE SLIDE. THE POST DOCK WORKING ON THIS ACTUALLY IN PIP WIT PARTNERSHIP WITH THE DISEASE FOUNDATION. JUVENILE OR J.M., TRAVIS ACTUALLY EX FORWARD THIS THE INCOMPETENTER FUR UM UP REGULATION THAT NEEDS TO MAJOR COMPATIBILITY COMPLEX AND DOWNSTREAM INFLAMMATORY MUSCLE CELLS TO DEVELOP USING GENOME EDITING APPROACHES A REPORTED SYSTEM TO DISCOVER NEW SMALL MOLECULES, MODULATING THIS PATHWAY SO SCREENING IS UNDER WAY. OBVIOUSLY THIS IS BEEN DONE IN PARTNERSHIP WITH PRINCIPLE INVESTIGATORS ON THE OUTSIDE WORKING ON THIS DISEASE. HAVING STUDIED THE BIOLOGY FOR SOMETIMES 20 OR 30 YEARS, UTILIZING FOR TECHNOLOGY AND AUTOMATION APPROACHES WITHIN D.P.I. OVER 20,000 MOLECULES HAVE BEEN TESTED IN THIS NEW ASSAY APPROACH AND THE PROJECT IS STILL ON GOING MANY OF THIS IS AN EXAMPLE WE'RE DOING RIGHT NOW. SO THIS IS NOT GO UNNOTICED BY THE PATIENTS, THEIR FOUNDATION, THEY'RE FORMER DIRECTOUR CHRIS AUSTIN, WAS ACTUALLY RECOGNIZED BY THE PRESIDENT OR EXECUTIVE DIRECTOR AS PART OF THE RARE DISEASE STATE. THESE ARE IMPORTANT PARTNERSHIPS BECAUSE AND SO, IF YOU ARE ACTUALLY EMBARKING ON THE JOURNEY IN THIS SPACE AND DEVELOPING THERAPY, YOU NEED AMOUNALLTHE SUPPORT FROM YOUR STAKEHOLDERS AND I'M LEAVING A LOT OUT OF THESE STORIES. NATURAL HISTORY STUDY AND SO ON AND I WILL MOVE ON TO GIVE YOU ANOTHER EXAMPLE OF A RARE DISEASE WHERE WE ACTUALLY WORK WITH CHILDREN'S HOSPITAL ON ANOTHER RARE DISEASE TO ADVANCE AN ACTUAL CANDIDATE THERAPY TO THE STAGES SO THIS IS THE AUTOIMMUNE OR PATH, REALLY NOT A SIMPLE DISEASE TO DESCRIBE AND REALLY, I HAVE TO APOLOGIZE FOR THE IMAGES ON THE RIGHT SIDE ON THIS SLIDE AND IT'S ACTUALLY ANNA ACCUMULATION OF SERFACTIN IN OF THINGS O THE LUNGS OF THESE PATIENTS WHICH LEADS TO RESPIRATORY FAILURE. THEIR MACRO FAY GEES ARE NOT THERE. SO THE TREATMENT RIGHT NOW IS CALLED LUNG LAVAGE UNDER GENERAL ANESTHESIA. THESE PATIENTS ARE PUT UNDER AND THEIR LUNGS ARE FLUSHED WITH SALINE WITH THE CLINICIAN HE'S OBSERVING THE THEY SEE CLEAR AND THEY STOP THE PROCEDURE AND YOU CAN ACTUALLY SEE THIS IN ACTION IN AND LINK DOWN BELOW AND VERY INVOLVING PROCEDURES AND EXTREMELY SO, IT ACTUALLY WORKED ON MY CANDIDATE DRUG REVERSE THESE ACCUMULATION SERFECTIN IN THE LUNGS OF THESE PATIENTS BY USING THIS DRUG CANDIDATE G.M. BIOLOGIC IN THE FORM TO BE USED AFTER BONE MARROW TRANSPLANTS AND THE TEAM HAD WORK ON RELATION FOR ADMINISTRATION ROUTE OF THIS DRUG AND DEVELOPED THE RELEVANT PACKAGE PER N.D.A. REQUIREMENTS AND IMPORTANTLY, WITHIN THE LABS WE DO A LOT OF WORKER IT WILY AND IT'S NOT ALL OF THE WORK AND SOME OF THE WORK THAT IS LATE STAGE IND ENABLING WITH THE TRULY WASTEFUL TO DO INTERNALLY BECAUSE, HE WOULD BE REALLY A WASTE OF TAXPAYERS' MONEY TO SET UP ENTIRE ANIMAL FACILITY FOR JAIL TOXICOLOGY STUDYING, GIGANTIC MANUFACTURING FOR DIFFERENT THERAPEUTIC CANDIDATES SO WE DO A LOT OF THIS WORK TO CONTRACTS WHILE STILL HAVING EXPERTS IN FIELDS SUCH AS G.O.P. TALKS WITH CLINICAL TALKS AND CMC IN-HOUSE TO THESE PEOPLE DO A LOT OF THEIR WORK THROUGH CONTRACTS AND YOU WILL ACTUALLY SEE TOMORROW A CONTRACT TOPIC AS A CLEARANCE TOPIC FOR YOU TO REVIEW AND PROVE TO ALLOW D.P.I. TO CONTINUE TO UTILIZE CONTRACTS FOR THIS WORK TO BE MOST EFFICIENT AND PLEX ABLE. THIS SAID, THE TEAM ACTUALLY, DEVELOPED THE FORMULATION AND DEVELOPED THAT ACTIVE PACKAGE AND THAT A LOT OF TIMES THE AS SET REALLY IS LEFT CURBSIDE FOR OTHER DOWNSTREAM REASONS AND CLINICAL TESTING IS NOT INITIATED. SO IN THIS CASE, THE SEAN I HIGHLIGHT THIS PROJECT IS WE ACTUALLY INVOLVE PRACTICALLY EVERYBODY IN EXTRAMURAL COLLEGE AND THE DIVISION OF -- THE NETWORK AND THE ALLIANCES, GRANTS MANAGEMENT, OR BUDGET OFFICE PARTNERS TO RAPIDLY ACCELERATE AND CLEAN OUT TRIAL AND IT WAS JUST PREPARING THE I.N.D. PACKAGE AS NOT ENOUGH SO REALLY, THIS IS THE NETWORK WE WERE ABLE TO CREATE INCLUDING IF YOU LOOK AT THE UPPER RIGHT THROUGH THE RED DISEASES CLINICAL NETWORK AND FROM THE OFFICE OF RARE DISEASES ATEN CATS YOU ENROLL THE PATIENTS AND HAVE THE TEST AS THERAPY SO AGAIN, WE'RE WORKING REALLY HARD TO BRING ALL THE STAKEHOLDERS TO THE STABLE AND NOT JUST BE ONE LAB CREATING ONE MARROW SOLUTION THAT SOMETIMES OR OFTEN TIMES DOESN'T GO ANYWHERE AND SO, THE LAST EXAMPLE IN THIS SPACE IS THIS TRULY, I WOULD SAY, VIRTUAL OR INFORMATICS OR BIOINFORMATICS, WHATEVER YOU WANT TO CALL IT, THE EXAMPLE OF THE CURE I.D. APP. WE'RE CAPTURING CROWDSOURCING EXPERIENCES OF NOVEL NEWS OF EXISTING DRUGS. THIS STARTED AS A PILOT EFFORT TO BETTER UNDERSTAND CLINICIANS EXPERIENCES WITH TREATING UNTREATABLE, OFTEN TIMES, NEGLECTED TROPICAL DISEASES IN DEVELOPING COUNTRIES AND OUT OF THIS INITIAL EFFORT GROUP THIS CURE I.D. APP SUPPORTED NOT JUST WITHIN THE D.P.I. AND THE LABS BUT ALSO F.D.A. AND IT'S APART FROM THE WORLD HEALTH ORGANIZATION OTHERS REALLY ASKING CLINICIANS TO. I DON'T HAVE TIME TO GO OVER THIS IN DETAIL. I WANT TO HIGHLIGHT THE FACT THAT WIR WE'RE EXPAND THIS TO CALLED 19 SURVEILLANCE FROM MEDICAL RECORDS COLLABORATING WITH N3C, JOHNNY PROVIDED INTRODUCTIONS TO N3C EARLIER AND ALSO WITH THE CRITICAL FACT SO REALLY THIS IS THE JOURNEY SORT OF BACKWARDS AND IT HOPEFULLY WILL ENABLE D.P.I. TO COME UP WITH NEW THERAPEUTIC-TYPE OFFICES SO WE CAN TEST IN THE LABS BASED ON WHAT CLINICIANS HAVE SEEN WITH THEIR PRACTICE AND SO, I MENTIONED THE OTHER WHICH IS ENGAGING MULTIPLE DISCIPLINES IN THE AREAS OF EXPERTISE TO DRIVE INNOVATION. A LOT OF YOU KNOW WITHIN THE ACADEMIC WORLD, THIS IS EASIER SAID THAN DONE. THERE ARE MANY DIFFERENT DEPARTMENTS AND THERE ARE DIFFERENT BUILDINGS AND EVERYBODY IS APPLYING FOR THEIR OWN GRANTS. YOU MIGHT HAVE A GREAT DISCOVERY WITHIN YOUR CELL BIOLOGY EFFORT TO TACKLE IT BUT YOU DON'T HAVE A PARTNER IN CHEMISTRY TO DESIGN THE MOLECULE. IT WOULD ACTUALLY TACKLE THE DISEASE IN YOUR STUDY. WE HAVE ALL OF THIS UNDER ONE ROOF AND WE'RE ACTUALLY TRYING TO BRING EVEN MORE AREAS OF EXPERTISE OR DISCIPLINES TO BEAR. I WANT TO GIVE YOU A FEW EXAMPLES OF THIS. MULTI DISCIPLINARY TEAM APPROACHES TO THE CREDIT ACTIVITY OF INVITO TEST, THE 3-D TISSUE FABRICATION THAT JOHNNY MENTIONED EARLIER AND THE OTHER EXAMPLE IS THE DESIGN AND TESTING DESIGN SYNTHESIS IN TESTING OF NEW MODELS AND YOU ENABLE CUTTING EDGE THERAPIES FOR PREVIOUSLY ON THE REST DISEASES AND UNDER STUDY PATHWAYS. FOR AUTOMATED CHEMICAL IN THIS PROGRAM. JOHNNY GAVE AN INTRODUCTION TO OUR 3-D LAB. I WANT TO FOCUS ON THIS AGAIN, ONE MORE TIME TODAY, BECAUSE IT'S REALLY A GREAT EXAMPLE OF BRINGING EXPERTISE FROM VERY DIFFERENT DISCIPLINES THAT YOU DON'T NORMALLY FIND UNDER ONE ROOF. REALLY, THIS IS THE AMPLIFIER EFFECT HERE AT THE LABS. SO THE GOAL HERE IS TO BUY FABRICATE THREE-DIMENSION ISSUE MODELS THAT HOPEFULLY THEY RECAPITULATE TO DISEASE PATHOLOGY AND THERE ARE MORE PREDICTIVE TO CLINICAL ADVOCACY OR EXISTING THE MOLECULES. REALLY IMPORTANT PROBLEMS UTILIZING HUMAN CELLS. THIS REQUIRES THE COMBINED EXPERTISE AND EFFORTS TO A VERY DIFFERENT DISCIPLINES. CELL BIOLOGY, TISSUE EXPERTS, BIO NOT GUINEAR SCIENTISTS, OPTICAL ENGINEERS, SO ULTIMATELY ULTIMATELY, THE GOAL OF THIS LAB WITHIN D.P.I. IS INFORM TO INTEGRATE THE ISSUES OF THESE MODELS IN DRUG DISCOVERY EFFORTS SO THINK ABOUT AND REALLY IMPLEMENT THE PRINCIPLES OF THREE Rs, REPLACE, REDUCE AND REFINE THE USE OF ANIMALS THIS THIS SEARCH. SO JOHNNY SHOWED DOWN BELOW EARLIER AND WE REALLY THINK THAT THIS IS FIRST THE LAB AT THE DEVELOPING THE NORMAL OR HEALTHY WILD TYPE ISSUE IN COLLABORATION WITH EXPERTS IN THAT PARTICULAR ISSUE. JOHNNY GAVE THE EXAMPLE OF SKIN. WE HAVE MANY OTHER EXAMPLES WITHIN THIS LAB. YOU VALIDATE THE PERFORMANCE OF THIS PRODUCT, THE 3-D BIO PRINTED ISSUE, TO VARIOUS MEANS AND OUR HOPE IS TO ENGAGE DISEASE EXPERTS TO BUILD DISEASE MODEL BASED ON THE TISSUE. AN EXAMPLE WAS SKIN GIVEN EARLIER AND I'LL GIVE ANOTHER EXAMPLE LATER. IT'S TO TREAT THESE. FOR INSTANCE, THE TISSUE WITH DRUG CANDIDATES ENVIRONMENTAL MOLECULES OR WHATEVER AND THE NEGATIVE EFFECT AND TOXIC EFFECT TO BETTER INFORM DECISION-MAKING BY THOSE WHO KNOW THESE THERAPIES, IT'S NOT AS SIMPLE AS IT LOOKS. IT'S NOT JUST WHERE THINGS SELL AND BUILDING SKIN PLAYERS AND SO ON. THIS IS WHY WE NEED HOW DO WE EFFECT THESE IN THESE ISSUES EQUIVALENCE. I DON'T HAVE TIME TO GO OVER THESE DETAILS RIGHT NOW AND I HOPE THAT WE CAN REVISIT THIS STUFF IN THE FUTURE. JUST ONE EXAMPLE OF REALLY BUILDING TISSUE MODELS FOR COVID-19, LOOKING AT THE VARIOUS ORGANS AFFECTED BY SARS-CoV-2, OBVIOUSLY WE WANT TISSUES AND FIRST AND FOR MOST IF THERE ARE OTHER TISSUES HERE AND REALLY APPROPRIATE END POINTS TO MEASURE THE TREATMENT WITH THE VIRUS AND POTENTIAL THERAPEUTIC MOLECULES. SO, THIS IS REALLY HOW WE THINK THIS EFFORT AND IT'S A GREAT EXAMPLE OF US ACTUALLY ENGAGING, NOT JUST SELL BIOLOGY EXPERTS AND DISEASE EXPERTS BUT ALSO BIOMEDICAL ENGINEERS, OPTICAL ENGINEERS AND A LOT OF THESE IMAGES ARE PRODUCED TO A NOVEL SUCH AS TISSUE CLEARING, AND OTHER IMAGING APPROACHES. BECAUSE THESE SYSTEMS ARE NOT READILY OBSERVABLE OR MEASURABLE BY USING EXISTING INNS MENTATION. THIS IS REALLY WHERE REALLY HELPING TO BRING MULTIPLE PARTIES TO THE TABLE AND WE ALSO UTILIZE SMALL BUSINESS. WE'RE NOT TRYING TO FLY THIS THING SOLO. SO, ANOTHER EXAMPLE IN THIS SPACE IS REALLY FROM THE WORLD OF CHEMISTRY, REALLY. WE LOOKED AT THIS MAYBE SEVEN OR EIGHT YEARS AGO AND LOOKED AT IT AGAIN AND AGAIN. THIS IS ADMITTEDLY A VERY AWKWARD INTO SPACE AND A LOT OF AUTOMATION, COMPUTER SCIENCE IS INJECTED INTO BIOLOGY INFORMATICS AND ENGINEERING AND ALLOWING PEOPLE TO ASK VERY DIFFERENT QUESTIONS, LARGER-SIZED QUESTIONS AND PAINTING LARGER AND MORE USEABLE OR USEFUL ANSWERS. WITH CHEMISTRY, AND AGAIN P. I KNOW I'M EXAGGERATING THE EXAMPLES, RELATIVELY LITTLE HAS CHANGED IN TERMS OF HOW PEOPLE ACTUALLY GO IN THE LAB AND MAKE NEW MOLECULES. THAT IS THE CHEMICALS SYNTHESIS SHOWN ON THE VERY FAR-RIGHT. AND I'M GOING TO ELABORATE ON THIS EXAMPLE FURTHER. SO, REALLY, REALLY, THIS IS NOT NEW AND IT WAS NOT NEW WHEN WE STARTED THIS THOUGHT PROCESS BECAUSE HOW TO ACTUALLY ACCELERATE THE EVOLUTION OF CHEMICAL SYNTHESIS AND INTEGRATE IT WITH THE REST OF THIS PROCESS AND EARLY, PRE CLINICAL DISCOVERED. THERE WERE A LOT OF EFFORTS BY GROUPS A COUPLE YEARS AGO WHO LITERALLY CAN WE WORK ACROSS EN CAT, NOT JUST WITHIN THE LABS BUT OUR EXTRAMURAL COLLEAGUES TO ADVANCE THESE FIELDS AND HOPEFULLY DESIGN SOLUTIONS FOR THESE TRANSLATIONAL PROBLEMS SO THIS WAS AN EFFORT BY BOTH D.P.I. PEOPLE OUR DIRECTOR BACK THEN CHRIS AUSTIN AND ALSO THE OFFICE OF SPECIAL INITIATIVES, DAN, AND OTHERS WHO REALLY THINK ABOUT A NEW PROGRAM IN THIS SPACE WHICH WAS INITIALLY FUNDED BY THE ACCELERATION NETWORK AND TO ADVANCE CHEMISTRY AND RELATED EFFORTS TO ENABLE REALLY BIOLOGY BIOLOGY, CHEM TREE, ENGINEERING TO GIANT TO AUTOMATE THE DESIGN GENERATION AND TESTING OF NEW MOLECULES. WE CALL THIS INITIATIVE ASPIRE, STANDS FOR SPECIALIZED PLATFORM FOR INNOVATIVE RESEARCH EXPLORATION AND THERE WAS ACTUALLY DIFFERENT NAME EARLIER SUFFICE IT TO SAY IT WENT TO A LOT OF PREPARATIONS AND DISCUSSIONS WITH OUTSIDE STAKEHOLDERS INCLUDING -- AND REALLY THE RIGHT SIDE OF THIS SUMMARIZES IT'S REALLY ALL ABOUT INTEGRATING CHE CHEMISTRY, PLANNING A NEW MOLECULES AND DESIGNING AND SYNTHESIZING NEW MOLECULES AND INTEGRATING THAT WITHIN ITS TESTING FOR IN INTENDED WITH DATA RESULTING FROM SET TESTING GUIDING DESIGN IS A BETTER VERSION OF THAT MOLECULE. SO LOOKING MORE CLOSELY, OF COURSE, THERE'S A LOT OF ADDITIONAL STEPS HAVE TO BE CONSIDERED AND REALLY THE TEAM THAT HAS BEEN ASSEMBLED AND IS STILL ACTUALLY UNDER ASSEMBLY AND DEVELOPMENT AT THE LAB IS FOCUSING ON REALLY THE STEPS INVOLVING THE DESIGN OF MOLECULES, BETTER PROCESSING OF EXISTING DATA. WE KNOW FROM CHEMISTRY RESEARCH A LOT OF NEGATIVE DATA WERE NOT RECORDED AND NOT EASILY CAPTURED AND ON THE MACHINE SIDE, ITEMS 2, 3, 4, IN THIS DIAGRAM, HOW DO WE ACTUALLY VIEW IT MECHANICALLY? WE ACTUALLY ARE WORKING WITH A LOT OF STAKEHOLDERS IN CHEMICAL INDUSTRY AND SOMETIMES MALL BUSINESSES WHO EFFECT AUTOMATION VARIOUS CHEMICAL STEPS. WHETHER IT'S SYNTHESIS OR REACTION WORKUP, ISOLATION, AND THEN UTILIZING OUR OWN RESOURCES AND EXPERIENCING AUTOMATION AND SCREENING WE'RE CLOSING THE LOOP IN TERMS OF AUTOMATED BIOLOGICAL TESTING AND INFORMING WHAT HAPPENS TO THESE NEW MOL RULES MOLECULES COULD THEY CAN HELP CHEMISTS BETTER DESIGN NUANCE SO THIS IS ALL GOING TO BE PUBLIC FENCING AND WE'RE ALREADY ENGAGING MULTIPLE STAKEHOLDERS NOT JUST IN TERMS OF MULTIPLE DISCIPLINES BUT IN TERMS OF INTRAMURAL PARTNER WHAT IS EXTRAMURAL AND THIS IS IMPORTANT. YOU WILL EAR THIS OVER AND OVER AGAIN AND WE'RE REALLY TRYING TO REREMOVE SILOS WORKING WITH OUR EXTRAMURAL COLLEAGUES TO BUILD JOINT TEAMS WHO SOLVE THESE PROBLEMS. SO, MOVING ON, TEACHING OTHERS. SO THERE ARE MANY ASPECTS TO THIS AND AGAIN I DON'T HAVE TIME GO OVER EVERYTHING. I MENTIONED SOME OF OUR PRODUCTS. A LOT OF THESE FINDING ARE READILY DISSEMINATED TO PUBLIC PATIENTS WITH OF WHICH WELL OVER 400 PAPERS THE PAST COUPLE OF YEARS AND THEY'RE ALL THERE AND THEY HAVE THEIR PATIENTS. WE CAN'T REALLY DISCLOSE EVERYTHING IN A VERY USER-FRIENDLY WAY WITHIN A JOURNAL PAPER. WE'VE DONE A LOT OF WORK IN THIS SPACE TO BUILD PUBLIC-FACING PLATFORMS AND I'M SHOWING JUST VERY, VERY FEW OF THOSE HERE AND WE ACTUALLY HAVE EFFORTS ELIMINATE THE DRUG GENOME AND THIS IS A SUPPORTED PROGRAM AND THIS IS PUBLIC-FACING BROWSER TO HELP THE COMMUNITY LOOK INTO UNDER STUDY GENE PRODUCTS AND THE 90 OR SO PERCENT OF PROTEINS AND NO ONE IS FUNDING THESE DAYS, AND NO ONE IS STUDYING THESE DAYS AND FOR WHICH THEY ARE PRACTICALLY NOT MODULATORS. THESE ARE LIKELY GOING TO BE IN PARTNER IN MANY DISEASES SO HOW DO YOU ACTUALLY CATALYZE THE FEEL? DO YOU GO INTO THESE AREAS AND BE BRAVE AND APPLY FOR AN R01 GRANT AND GET SOME PRELIMINARY DATA TO STUDY THESE? THE LIST IS ACTUALLY VERY LONG AND I'M NOT GOING TO GO OVER ALL OF THESE THAT JUST A SECOND EXAMPLE OF A DIFFERENT KIND. THE ASSAY GUIDANCE MANUAL AND THIS WHAT IS IT NOW? IT'S 1400 PAGES OF NO HOW HOW TO ANALYZE SCREENING DATA AND HOW TO LOOK FOR ARTIFACTS? HOW TO AVOID ARTIFACTS? HOW TO PROGRESS A PROJECT THROUGH THE PRE CLINICAL SPACE. WE'RE MAKING ALL OF THIS PUBLICLY AVAILABLE THROUGH A VERY ROBUST, INTERNAL EDITORIAL AND ALSO EXTERNAL-THEMED TREATED AND THE LIST CONTINUES. WE ALSO MADE A LOT OF MACHINE INTELLIGENCE, MACHINE LEARNING APPROACHES OR PREDICTED MODELS AVAILABLE FOR OTHERS AND ANOTHER IS TRAINING OTHERS. INITIALLY D.P.I., THE LABS WE DIDN'T HAVE A WELL ESTABLISHED TRAINING PROGRAM SO BACK IN 2018 WE HIRED THE TRAINING DIRECTOR AND SHE ACTUALLY MOVED ON TO LEAD THE ENTIRE TRAINING EDUCATION FOR ALL OF NCATS NOW AND WE HAVE Dr. MARCUS HODGES IS OUR TRAINING DIRECTOR AND SO WHAT IS BEING PRODUCED HERE IN ADDITION TO JUST TRAINING PEOPLE AND GRADUATING THEM AND MAKING SURE THEY HAVE EXPERIENCE WITHIN THE D.P.I., JOHNNY MENTIONED THE CASE STUDY, THE TRAINING COURSE ON PRE CLINICAL TRANSLATION. THIS IS AN INTERESTING EXAMPLE BECAUSE IT ACTUALLY INVOLVES -- YOU CAN ARGUE A HOMEGROWN PROJECT BUT AGAIN IT'S A COLLABORATION, ALL RIGHT. IT'S NOT REALLY HOMEGROWN BUT IT'S DEVELOPED. SO IT AFFECTS CANCER BUT SUPPRESS METASTASIS. A LONG STORY AND WHY WANT TO ELABORATE IT NOW BUT IT WAS ACTUALLY DISCOVERED THROUGH AN BIAS CREAM AND D.P.I. SO THE WHOLE STORY OF IT FROM EARLY DISCOVERY TO DEVELOPMENT, ALL THE WAY TO PARTNERING WITH NCI TO ENABLE CLINICAL TESTING OF THIS MOLECULE IN PARTNERSHIP WITH Dr. RUDELOF AT NCI IS SUBJECT TO THIS TRAINING COURSE BECAUSE WITH SUCH A PROJECT YOU CAN ACTUALLY SEE, EVALUATE, DISSECT, THE MULTIPLE PROBLEMS IN TRANSLATION AND NOT JUST THE CREAM AND HOW YOU ANALYZE THE DATA AND HOW YOU START CRITICAL TESTING IF YOU ARE FINAL MOLECULE AND EVERYTHING IN BETWEEN, INCLUDING PROBLEMS WITH PARTNERING, INTELLECTUAL PROPERTIES, MAKING SURE ALL THE PARTIES ARE ALIGNED SO THIS IS A REALLY GOOD EXAMPLE IF WE'RE USING TO TRAIN THE FUTURE TRANSLATIONAL RESEARCHERS TEACHING OTHERS HOW TO FISH. RECENTLY, OUR EDUCATION TRAINING GROUP PUBLISHED A PAPER ON THE OUTCOMES FROM OUR INTRAMURAL TRAINING PROGRAM AND WE'RE ABOUT TO PUBLISH A PAPER AGAIN JOINTLY WITH OUR EDUCATION AND TRAINING TOLL ON THE GROUNDS ON THE ON THE TRAINING OF N CATS. LAST BUT NOT LEAST, WE HAVE PLANS FOR SUMMER INARE NOT DIVERSITY COHORT IN NEXT SUMMER AND DELAYED BY COVID. WE STARTED IT THIS SUMMER BUT WE'RE STARTING IT NEXT YEAR DECREASING THE IN THE TRAINING COHORT THAT GOES TO D.P.I. AND JOHNNY MENTIONED THE TRANSLATIONAL SCIENCE INTRA AGENCY FELLOWSHIP AND THIS IS REALLY IMPORTANT AND THIS IS THE FIRST YEAR PARTNERING WITH NDA AND I HAVE TO ACTUALLY TAKE A STEP BACK AND RESPOND TO SOME OF THE COMMENTS AND FOLLOWING THE PRESENTATION ON THE D. P.I. CHOICE PARTNER WITH THE F.D.A. AND MANY, MANY YEARS AND IT ACTUALLY STARTED BACK IN 2008-2009 AND THE PROGRAM ADVANCING TOXICOLOGY YOU BETTER UNDERSTAND CLINICAL INDIVIDUAL PRODELS WHO COULD BE ASSIST IN THE INVIVO AND LATER ON WITH THE THEY ARE PEWS I CAN FOR RARE AND NEGLECTED DISEASE PROGRAM OR TREND BACK IN 2009 AND 2010 BEGAN PREDATING N CATS WE STABBED A WORKING GROUP WITH THE FDA TO ENABLE BETTER MUTUAL UNDERSTANDING OF THESE PROJECT FOR DISEASES AND TO SEE NATURAL HISTORY STUDY AND RELATED AND IT REALLY FAST FORWARD TO TODAY WE'RE STARTING THIS INTRA AGENCY FELLOWSHIP WITH THE FDA AND REALLY WITH THE GOAL AND CONNECTING ORGANIZATIONAL UNITS OF HHS, WE HAVE THREE FELLOWS STARTING WITH US NOW SO THIS IS YEAR ONE AND REALLY THE GOAL IS TO PROVIDE TRAINING INTRAIZATIONAL SCIENCE AND D.P.I. AT N CATS AND REGULATORY SCIENCE AND F.D.A. AND THE GOAL BEING WHO WORKED TOWARDS SOLVING REGULATORY SCIENCE PROBLEMS AND IN THESE THREE INITIAL FELLOWS WILL WORK EXACTLY IN THIS SPACE AND REPURPOSES FOR INFECTIOUS DISEASES AND HOW THIS CROSS TOPS THE REGULAR TOWARDS SCIENCE AND TRANSLATIONAL RESEARCH AND THOUGHTS OF JOHNNY MENTIONED THIS AND HOW WE ACTION AND ENABLE THIS FIELD AND FOR RARE DISEASES TO BE BETTER ACCEPTED AT F.D.A. AND TO MAKE THE COST OF GOODS LOUDER AND LAST IF NOT LEAST, RELATED TO THE EFFORTS IN D.P.I. AND F.D.A. ALREADY IS VERY INTERESTED IN SKIN MODEL FOR DRUG CANDIDATES AS WELL AS AS WELL AS MODEL TO ITS A PROGRAM AND HOW CAN PRE CLINICAL RESEARCH AT N CATS BE BEST PUT TO USE AS FAR AS CREATING USEFUL DATASETS TO ACT ON YOU CAN ONLY VIEW IT WHEN YOU WORK TOGETHER WITH THE FDA, NOT BEFORE YOU GO TO F.D.A. SO WE'RE REALLY HOPEFUL THAT THIS WILL IS AND DEFINITELY AND IT'S INVESTED AND THE LAST POINT IS THE RESPONSE TO THE PUBLIC-HEALTH EMERGENCIES. REALLY, THE CULTURE, D.P.I., THE N CAT LAB, THE LONGSTANDING PRINCIPLES THAT SCIENCE HAS ENABLED US TO RESPOND TO THESE PUBLIC-HEALTH EMERGENCIES, YOUR EYES ARE PROBABLY FOCUSING ON COVID-19 FROM THE SLIDE AND LET ME START FROM THE TOP BULLET, REALLY. THE GULF OF MEXICO, OIL SPILL, THIS REDATES N CATS, RIGHT. THE GROUP WAS ASKED TO EVALUATE THE CANDIDATE DISBURSEMENTS THAT IS USED IN THE GULF OF MEXICO COULD CONTAIN THE OIL SKILLS AND THERE WAS NO TIMELY TO DEVELOP SUCH DATA AND THE CLOCK WAS TICKING ON THE SCALE OF THE HOURS AND DAYS AND NOT MONTHS OR YEARS SO, LONG STORY SHORT, A SENIOR COVID THAT MEMORIAL DAY WEEKEND TO BRING THE CANDIDATE DISBURSEMENTS AND THE LAB AND FOR MANAGEMENT TEAMS WITH THESE MOLECULES AND PREPARED PLATES FOR TESTING AND THE TEAM AND RELATED AS SAYS AND RAN THESE TESTS LITERALLY IN THE TIME SPAN OF JUST A FEW DAYS AND DELIVERING THE DATA TO THE E.P.A. AND IMMEDIATELY AND THE OVER ALL REPORT INCLUDED REPEAT BESTING AND WITHIN 30 DAYS AND THE DATA WORK PUBLISHED AND 30 DAYS AND SO IS THE BUILT E.P.A. HAD DATA FROM US TO RELY ON AND NOT OTHER WAYS TO GENERATE ANY OTHER DATA ON THAT TIME SCALE AND SO WE ROSE TO THE OCCASION THAT THIS IS THE CULTURE OF N CAT'S D.P.I. WE TURNED ON A TIME AND WE WORKED WITH OTHERS TO RESPOND TO PUBLIC-HEALTH EMERGENCIES AND EBOLA, ZIKA, WE DON'T NEED TO GO INTO DETAILS. THE GROUP HERE HAS EXECUTED WELL OVER A DOZEN DIFFERENT TITLE GROUP JONES AND VARIOUS PROJECTS AND THESE HAVE BEEN PUBLISHED VERY RAPPEDLY AND ALLOWED OTHERS TO TEXT THE CANDIDATE MOLECULES TO ADVANCE MODELS AND OPEN CRISIS, WE TOUCHED ON THIS HEAL INITIATIVE AND D.P.I. TEAMS ACTUALLY RECEIVED MULTI-YEAR FUNDING TO ENGAGE IN THESE MANY DOZENS OF COLLABORATIONS IF YOU DEVELOP AND DES SEM NATURE AND CANDIDATES FOR THE OVERDOSE AND LAST BUT NOT LEAST, COVID BEGAN, THIS IS BEEN REALLY A MULTI PRONGED RESPONSE TO SET UP AND RUN DRUG REPURCHASING SCREENS TO LEVERAGE OR EXISTING INFRASTRUCTURE TO DEVELOP NEW TEST SYSTEMS AND IF YOU REALLY PARTNER WITH A WIDE RANGE OF STAKEHOLDERS ADVANCE LATE-STAGE DRUG CANDIDATES, INCLUDING OTHER CENTERS, IT SHOWED THE DATA PROPERTIAL THAT YOU CAN GO THERE TO SEE WHAT WE'RE DOING IN THIS SPACE AND BEGAN IN THIS INCLUDES DATA VARIANTS, NOT JUST INTERNAL SCREENING DATA OR OTHER DATA. I HAVE TO REALLY THANK MANY PEOPLE WITH N CAT D.P.I. FOR DECIDING TO FOREGO DETAILED PUBLICATION FINDINGS JUST SO WE CAN POST THE SCREENING DATA IN REAL TIMES AND A LOT OF RESEARCH OUT THERE CONDUCTED THE SEARCH THAT THEY TAKE THEIR TIME TO CRAFT THE PERFECT PAPER BECAUSE THAT IS REALLY WHAT COUNTS IN ACADEMIA FOR EXAMPLE. HERE, WE'RE REAM' POSTING DATA IN NEAR REAL TIME BECAUSE WE'RE A FEDERAL LAB AND AND WE'RE RESPONDING TO PUBLIC-HEALTH EMERGENCIES AND EMERGENCY IN THIS CASE IN THE MOST RAPID FASHION. I WANT TO STOP HERE. REALLY THANK EVERYBODY, D.P.I. AND THE REST OF N CATS. YOU MUST HAVE DETECTED AND THEY ARE AND THEY'RE GOING TO BE ALBERTA OF PARTNERSHIPS WITHIN N CATS AND WE'RE TRYING TO CHURCH THESE LINES BETWEEN INTRAMURAL AND TRA MURAL TECHNOLOGY TRANSFER GRANTS MANAGEMENT IN SOLEMN AND WE WORKED WITH THE NIH WITHOUT AND OUTSIDE NIH AND IT'S ACTUALLY BEING DONE OR HAS BEEN DONE IN PARTNERSHIP WITH PRIVATE SECTOR, SMALL COMPANIES, SOMETIMES LARGE COMPANIES SO WE WORK WITH EVERYBODY. YOU CAN LEARN MORE ABOUT WHAT WE DO WITHIN D.P.I. AND ON THIS WEBSITE AND I LOOK FORWARD. >> THANK YOU VERY MUCH, ANTON. WE HAVE A COUPLE OF QUESTIONS IN THE CHAT. THAT SOME OF OUR OTHER STAFF ANSWERED. I WANTED TO SEE, Dr. SHIREMAN, DO YOU WANT TO ADD TO YOUR QUESTION OR WAS THE RESPONSE ADEQUATE? >> IT WAS A GREAT RESPONSE. I DO THINK, OF COURSE, THE N CAT STAFF TOUCHED ON THE ETHICAL ISSUES OF HOW DO YOU PROTECT PATIENT PRIVACY ESPECIALLY WITH GENETIC INFORMATION WHICH ESSENTIALLY YOU CAN'T BECAUSE OF THE TYPE OF INFORMATION. IT'S DIFFICULT FOR REGULATORY TO CATCH UP WITH THE TECHNOLOGIES THAT WE CURRENTLY HAVE. THEY'RE DOING THEIR BEST BUT YOU KNOW, MULTI SITE TRIALS AND EVERYTHING REGULATORY IS ALWAYS ABOUT A DECADE BEHIND THE INNOVATION WE HAVE A LODGE WAY TO GO MAKING THIS INTEGRATED DATA A REALITY? >> THANK YOU, Dr. BRAYDENBURG HAD A QUESTION ABOUT DISSEMINATION MODELS. DID YOU WANT TO ADD ANYTHING -- >> IT'S SO NICE TO CALL ME Dr. BRAYDENBURG, I'M JUST A JD. [LAUGHTER] >> IT'S NOT AN INSULT BUT IT'S JUST SO NICE. I WAS CURIOUS, THE DISSEMINATION YOU DESCRIBED IS LARGELY PUBLICATIONS AND I WONDER WHETHER THERE ARE MECHANISMS FOR AN ACTUAL TECHNOLOGY INTERSECTION THAT WOULD PERMIT ACCESS TO DATABASES OR ACCESS TO TOOLS OR ACCESS TO A SET OF TOOLS, SORT OF A MENU OF WHAT YOU CAN ACCESS TECHNICALLY TO ALLOW OUTSIDERS TO ACTUALLY USE THE TOOLS, OBVIOUSLY GIVE WHAT THEY LEARNED BACK TO YOU SO YOU CAN CONTINUE TO INFORM YOUR TOOL DEVELOPMENT BUT THAT'S MY QUESTION. IS THERE ANOTHER INTERACTION, ENGAGEMENT MODEL, DISSEMINATION MODELS? >> I WOULD SAY ABSOLUTELY. AGAIN, WHEN YOU PUBLISH THE PAPERS YOU HAVE TO FOLLOW A JOURNAL FORMAT AND SOMETIMES SUBSCRIPTIONS SO YOU ARE EXACTLY RIGHT. YOU CAN'T REALLY MAKE EVERYTHING VERY EASILY ACCESSIBLE THROUGH A PAPER. WE HAVE A LOT OF EXAMPLES WHERE WE'VE ACTUALLY MADE THINGS AVAILABLE BEFORE PUBLICATION AND A LOT OF TIMES IN CONVENTION WITH A PUBLICATION AND REALLY THE NCAT'S WEBSITE IS THE GO-TO PORTAL WHERE YOU CAN ACTUALLY NAVIGATE TO FIND THE VARIOUS TOOLS. THESE TOOLS INCLUDE NOT JUST DATABASES THAT ACTUAL BROWSERS, SOURCE CALLERS, PEOPLE CAN ACTUALLY DOWNLOAD SOFTWARE AND PRACTICE THE BETTER TRANSLATION WITHIN THEIR OWN LABS. IT'S TOTALLY UNINHABITED FASHION. THEY DON'T HAVE TO LICENSE SOFTWARE OR WHATEVER. THEY CAN SIMPLY DO IT. WE HAVE MULTIPLE SUCH EXAMPLES FROM THE WEBSITE WITH THE ASSAY GUIDANCE MANUAL, WE'RE ALSO TAKING THE APPROACH OF ACTIVE PUSH AS IN, LECTURES, ON-LINE FORUM TO DISSEMINATE THE FINDINGS AND TO BRING THE BEST PRACTICES TO EVERYBODY'S ATTENTION. THESE ARE WORKSHOPS, CLEARLY NOW WITH EVERYTHING HAPPENING. THEY'RE VERY WELL ATTENDED OR YOU HELP ALL OF THE SIGNED UP ATTEND'S ARE PAYING ATTENTION AND WE'VE SEEN LITERALLY QUADRUPLING OF ATTENDANCE TO THESE WORKSHOPS. ON BEST PRACTICES AND CLINICAL TRANSLATION, THEY FOLLOW DIFFERENT FORMATS, IT'S NOT ALL ABOUT ROBOTIC TYPES OF SCREENING AND WE COVER OTHER TOPICS AS WELL AND WE'RE TRYING TO EXPAND THE MENU WITH WHAT WE COVER TO ACTUALLY MEET THE NEEDS OF THE COMMUNITY. >> JOHNNY, DID YOU WANT TO ADD SOMETHING? >> I WAS JUST GOING TO ADD SOMETHING REAL QUICK. ANTON DID A FANTASTIC JOB ANSWERING THAT QUESTION AND I WANT TO GIVE YOU A SENSE OF SOME OF THOSE OTHER TOOLS AND TOOL KITS, FOR EXAMPLE, IN THE RARE DISEASE SPACE, N CATS HAS PULLED TOGETHER THROUGH THE OFFICE OF RARE DISEASES AND LED BY ANNE PARISSER PULLED TOGETHER RESOURCES FOR RARE DISEASE PATIENTS. ONE OF THE THESE IS THE GENETICS AND RARE DISEASE DATABASE AND IT'S ACTUALLY ONE OF THE TOP 10 RESOURCES A LOT THE AT THE NIH. A COMMON WELCOME BAC WEBSITE THAT'S VISITE D. THERE'S A PHONE LINE WHERE PATIENTS CAN CALL AND GET ADDITIONAL INFORMATION, FOR EXAMPLE, SO IT'S A REALLY WONDERFUL RESEARCH FOR THAT AND IT DESCRIBES IF THERE ARE CLINICAL TRIALS OR IF THERE ARE TREATMENTS FOR PARTICULAR RARE DISEASES AND EXPLAINS THEM IN LAY LANGUAGE, WHAT THOSE RARE DISEASES ARE SO IT'S BEEN ONE OF THOSE RESOURCES THAT HAVE BEEN VERY VALUABLE. YOU KNOW, THE OTHER -- THAT'S RESOURCE, THE OTHER PIECE OF IT IS DATA ITSELF AND WHEN WE MENTIONED THE OPEN DATA PORTAL, THAT REALLY IS VERY REAL TIME OF DATA THAT IS AVAILABLE WITHOUT GOING THROUGH PUBLICATION SO YOU CAN SEE THOSE DATA SORT OF INA PRE COMPETITIVE WAY, I GUESS, IF YOU CAN CALL IT LIKE THAT. AND THE OTHER RESOURCES IS FOR EXAMPLE, THE N3C WHERE YOU CAN ACCESS THAT AND SEE THE VARIETY OF DATA THAT ARE IN THERE AND THINK ABOUT WAYS TO USE THOSE DATA. OF COURSE, YOU CAN PUBLISH ON THAT AND CONTINUE THAT WORK FROM BEYOND THAT. BUT THOSE ARE SOME EXAMPLES I THINK OF IN ADDITION WHAT ANTON WAS MENTIONING. AND THEN THE CURE I.D. APP IS ONE OF THOSE OTHER BIG RESOURCE THAT'S IS ALSO A TOOL AND IT'S AN APP THAT WAS DEVELOPED TO HELP, YOU KNOW, BRING THIS IDEA OF CROWDSOURCING, WHAT PHYSICIANS ARE DOING IN TERMS OF TREATMENTS FOR A PARTICULAR DISEASES, USED MOST RECENTLY IN COVID, BUT REALLY USED FOR OTHER DISEASES AS WELL SO I THINK THERE ARE A COUPLE OF THINGS BUT, IF YOU HAVE OTHER IDEAS, I WOULD BE VERY INTERESTED IN HEARING WHAT YOU ARE THINKING ABOUT SOME OTHER IDEAS IN WHICH WE DID DO THINGS OUTSIDE OF PUBLICATION TO MAKE THINGS VEIL A IT'S A GOOD QUESTION AND MADE ME THINK QUITE A BIT. >> LET'S GO TO Dr. HARRIS. PAUL, YOU HAD A QUESTION IN THE CHATBOX. WOULD YOU LIKE TO RELAY THAT. >> I WAS JUST CURIOUS, YOU MENTIONED QUITE A NUMBER OF NIH ONLY AND PRIORITIZE RESOURCES. >> YEAH, SO, I WANT TO WORK BACKWARDS FOR LATE-STAGE PROJECTS. THESE ARE CLEARLY ENABLING STUDIES AND THEY'RE FOCUSED ON THE RARE DISEASES AND NOT EXCLUSIVELY SO. WE ACTUALLY VERY SPECIFIC APPLICATION MECHANISMS SO THIS IS KIND OF THE OTHER STRANGE ASPECT OF THIS. WE'RE AN INTRAMURAL GROUP THAT WE ACTUALLY UTILIZE SOMETIMES EXTRAMURAL LIKE PER REVIEW MECHANISMS SO WE ASKED A LOT OF THESE PROPOSALS THROUGH EXTERNAL EVALUATION FOR LACK OF A BETTER WORD. WE DON'T ISSUE GRANTS, WE DON'T AWARD MONEY, WE'RE DOING THE WORK OURSELVES. TO ACTUALLY HELP EVALUATE THE TECHNICAL READINESS AND OTHER ASPECTS OF THESE PROPOSALS, AND OBVIOUSLY, BECAUSE WE DON'T HAVE BANDWIDTH WE ENGAGE EXTERNAL EXPERTS TO EVALUATE THESE FOR HEALING INITIATIVE, SAME DEAL, WE ACTUALLY HAVE EXTERNAL REVIEWERS FOR THESE PROPOSALS. FOR SOME OF THE VERY EARLY STAGE COLLABORATIONS, A LOT OF THE REVIEW IS BASED INTERNAL LEON TECHNOLOGY, READINESS AND AREAS OF NEEDS AS FAR AS PORTFOLIO AREAS AND IT REALLY FOR THE LATE-STAGE PROJECTS AND AREAS WHERE WE ACTUALLY EXPECT EXTRAMURAL TO INTRAMURAL PARTNERSHIPS TO OCCUR. THEY'RE VERY SPECIFIC. THE REVIEW PROCESSES ARE THAT ARE ACTUALLY PLACED. SO, MY ANSWER IS SOMEWHAT FUZZY AND IT DEPENDS ON THE TYPE OF TRANSLATIONAL PROBLEM THAT YOU ARE TRYING TO SOLVE. WE HAVE DIFFERENT -- >> THAT'S HELPFUL. DOES THE GENESIS OF THE IDEA, IT USUALLY COMES FROM INSIDE? RATHER THAN FROM OUTSIDE? >> SO, YOU CAN THINK OF IT AS MEETING IN THE MIDDLE. WE KNOW A LOT ABOUT THIS SPACE AND THE PROBLEMS IN THE SPACE. WE KNOW ABOUT THE BIG BEENS IN TERMS OF PROBLEMS. WHAT WE DO NOT HAVE OURSELVES IS DISEASE EXPERTISE. WHAT WE HAVE OURSELVES IS KNOWLEDGE THE UNSTUDY GENE OR GENE PRODUCT. THAT'S WHERE WE ACTUALLY HAVE TO PARTNER. IF WE'RE THINKING A SPECIFIC AREA OF LET'S JUST USE A RANDOM EXAMPLE OF, I DON'T KNOW, CANCER METABOLISM, OR MAYBE IF YOU CAN CALL THAT A NEW AREA, IT WAS NEW 10 YEARS AGO ACTUALLY SO WHAT WE DID DO BACK THEN, AND DEVELOPED SMALL MOLECULES TO STUDY CANCER METABOLISM. SO THAT'S HOW YOU WANT TO THINK ABOUT IT. WE CAN DETECT, DEFINE, THE BIG PROBLEM AREAS THAT CAN SUBSTANTIATE A SOLUTION TO WORK ON THE PILOT PROJECT, WHATEVER IT IS WE ENGAGE OTHERS ON THE OUTSIDE. >> THANK YOU. >> SO WE'RE A LITTLE BIT OVER TIME. IF YOU COULD ANSWER TWO LAST QUESTIONS QUICKLY FROM Dr. RON GANATHAN AND Dr. KRETHLER. >> LONG TIME NO SEE. SO, I GUESS, HOPEFULLY THIS IS A SHORT QUESTION. I DIDN'T REALIZE WE WERE OUT OF TIME. I GUESS, I MAY HAVE MISSED IT ON THE SLIDES. CAN YOU SHARE WHAT YOUR ACTUAL SPEND IT PER YEAR? WHAT'S THE D.P.I. BUDGET WITH COUNCIL MEMBERS OR IS THAT CLOSE HOLD? >> I MAY BUDGET COLLEAGUES AND D.P.I. BUDGET IS ACTUALLY IT'S DIVERSE AND I CAN USE THAT WORD, ACTUALLY. WE HAVE THE PRO CREATED CONGRESSIONAL FUNDING. >> OK. >> I WASN'T WORRIED ABOUT THE DECIMALS SO MY QUESTION WOULD BE YOU'VE BEEN IN EXISTENCE FOR 10 YEARS SO IF IT'S 100 MILLION YOU'VE SPENT A BILLION DOLLARS, RIGHT, I MEAN IN THAT SENSE AND HOW DOES ONE THINK ABOUT THAT FROM A DRUG PERSPECTIVE SO YOU'VE TALKED ABOUT ALL OF THE THINGS THAT YOU PUT OUT THERE AND RESOURCES PHENOMENAL AND THE PROVOCATIVE QUESTION, SHOULD WE HAVE HAD A DRUG THAT IS ON THE MARKETPLACE BY NOW? >> SO WE HAVE, THAT NOT MIRED YET SO THIS IS THE MOSTLY IMMEDIATE RESPONSE TO YOUR QUESTION BUT I WANT TO GO BACK TO THE FUNDING, D.P.I. IS A STRANGE BEAST. THERE'S REALLY NO STEADY STAKE HERE. WHEN I SAID WE'RE APPROACHING 100 MILLION, IT'S PRESENT DAY INCLUDING SOME SOFT FUNDING. BACK 10 YEARS AGO, IT WAS MUCH, MUCH, MUCH LESS. CLOSE TO 30 MILLION OR SO. SO, WE'VE BEEN ON THIS TRAJECTORY. YOU CAN CALL IT FORMATIVE YEARS. THERE ARE A LOT OF DETAILS SORT OF HYPED THE SCENES OF HOW THE ORGANIZATION WAS FORMED. I TRIED TO GIVE YOU A LITTLE BIT OF INTRODUCTION TO THAT. A LOT OF INITIAL SUB UNITS OR UNITS OR PROGRAMS FOR LEGACY PROGRAMS FROM THE NIH COMMON FUND WERE FAULTED BETWEEN D.P.I. AND WE HAD TO MAKE THEM ALL WORK TOGETHER AND WORK SEAMLESSLY AND HERE WE ARE IN THE TENTH APP ANNIVERSARY. >> GIVEN IT'S OVER TIME, ANTON, MAYBE IT'S SOMETHING WE CAN COME BACK TO. I JUST PUT THAT OUT THERE AS A QUESTION FOR US TO THINK ABOUT IN TERMS OF METRICS OF PERFORMANCE FOR THE INTERMURAL PROGRAM AND PERHAPS SOMETHING FOR US TO REVISIT AS TO WHAT ELSE MIGHT WE SORT OF THINK ABOUT IN THAT SORT OF CONCRETE WAY THAT PEOPLE TEND TO THINK ABOUT AND INVESTMENT FROM A V.C. OR FROM A PHARMA COMPANY AS TO HOW MUCH WE MIGHT PUT IN AND HOW MANY DRUGS WE MIGHT GET OUT FOR THAT INVESTMENT, RIGHT. SO YOU KNOW, NUMBERS CAN VERY ALL THE WAY DEPENDING O HOW YOU DON HOW YOUDO THE ACCOUNTING AND THINK OF THAT NUMBER IN TERMS OF AN INVESTMENT TO GET A DRUG TO THE MARKETPLACE BUT THOSE WHO OF US WHO ARE IN INDUSTRY THINK ABOUT DRUG DEVELOPMENT PROJECT IF IT'S SUCCESSFUL, COSTING SOMEWHERE IN THE 100 TO 200 MILLION RANGE TO GET IT IN THERE SO THE QUESTION IS DO WE HAVE SUCCESS TO BANK ON. I'LL JUST ASK ONE FOLLOW-UP QUESTION. YOU TALKED ABOUT A FAIR NUMBER OF PATENTS THAT YOU HAVE IN ADDITION TO THE PUBLICATION, HAVE YOU REALIZED ANY INCOME, LICENSING INCOME FROM THOSE PATENTS? >> SHORT ANSWER IS YES. THERE HAS BEEN LICENSING REVENUE COMING IN. AGAIN, WE'RE FAIRLY A YOUNG ORGANIZATION SO A LOT PATENTS ARE BRAND NEW IT'S A PRACTICE AND THIS IS REALLY FEDERAL TRANSFER JOB AND I WANT TO GO BACK TO, I GUESS, THE QUESTION INVESTMENT AND N CATS REALLY DOES NOT HAVE TO MAKE DRUGS AND BE MEASURED BY DRUGS HERE IN THE MARKET. RIGHT. WE'RE NOT A PHARMACEUTICAL ORGANIZATION, WE'RE NOT A C.R.O., WE'RE HERE TO ADVANCE TRANSLATIONAL SCIENCES. WHEN YOU ACTION THE ACCOUNT FOR THAT DIMENSION TO ADVANCE TRANSLATIONAL SCIENCES, I WOULD SUBMIT TO YOU WE'VE BEEN PRETTY WELL, NOT EVEN THINKING ABOUT THE 44INDs, YOU CAN ACTUALLY HAVE DOLLARS BY THE INDs AND USE THAT AS A METRIC OR OTHER METRICS THAT REALLY DISSEMINATION, THE SOLUTION, TO COMMON TRANSLATIONAL PROBLEMS IN PRO CLINICAL SPACE AND OTHER TYPES OF METRICS. THEY HAVE TO BE TAKEN ALL TOGETHER, IN MY OPINION. >> THANK YOU. >> Dr. KRTZLER. CONSIDERING WE'RE OUT OF TIME, THE QUESTION WAS A SIMILAR DIRECTION. YOU HAVE A POWERFUL ENGINE AND EFFECTIVELY UTILIZING YOU WILL NOT HAVE TO WORK FROM START TO FINISH AS YOU INTERACT WITH YOUR STAKEHOLDERS AND YOUR COMMUNITY FOR SPECIFIC ELEMENTS AND PIPELINE AT A DIFFERENT TIME, NOT NOW, I'D LOVE TO HEAR WHAT THE MOST UTILIZED PART OF YOUR PIPELINE AND WHERE DO YOU DO THE HAND OFFS TO PARTNERS AND THAT ARE SIGNIFICANTLY MORE RESOURCES AVAILABLE WHEN IT GETS DOWN TO COMPOUNDS SCREENING AND IF YOU CAN DISCUSS THAT AT AN UPCOMING COUNCIL MEETING. >> THANK YOU FOR GREAT QUESTION. WE'RE OVER SUBSCRIBED THROUGHOUT THIS PIPELINE. I HAVE TO SAY. THERE'S REALLY NO-ONE PART THAT IS LESS OVER SUBSCRIBED SUCH AS FEDERAL CONTRACTING RULES AND SO ON. SOME OF THEM ARE SORT OF BEYOND THEIR ABILITY TO CHANGE TO BE HONEST WITH YOU. WHATEVER WE CAN CHANGE FOR THE BETTER, WE'RE ACTIVELY WORKING TOWARDS THAT. I'LL LEAVE YOU WITH THAT THOUGHT. >> GREAT. THANK YOU SO MUCH, ANTON, AND TO THE COUNCIL FOR THE GREAT QUESTIONS. WE ARE AT TIME, A LITTLE BIT OVER, WHICH MEANS THAT YOU KNOW, IF WE GO OVER TIME, THAT WAS A GREAT DISCUSSION WE HAD. AND I HOPE THAT IT GIVES YOU A PRETTY FIRM FOUNDATION ON THE GOALS AND THE MISSION OF N CATS AND WHO WE ARE AND HOW WE APPROACH THINGS SO THANK YOU FOR YOUR ATTENTION TODAY. I THINK BASICALLY FOR THE LAST SORT OF REMAINING ITEMS FOR THE DAY, WE WILL SEE YOU ALL TOMORROW AGAIN, VIRTUALLY, AND WE'LL RECONVENE AT 1:00 P.M. TOMORROW SO PLEASE, BE SURE TO CONNECT AT 12:45 TO MAKE SURE THAT EVERYTHING IS GOING OK. WITH THAT, I THINK I'LL GAVEL US OUT FOR THE DAY AGAIN AND GO TO MY VIDEO HERE. SO, THANK YOU SO MUCH AND WE'LL SEE YOU TOMORROW.