1 00:00:04,672 --> 00:00:05,773 GOOD MORNING. 2 00:00:05,773 --> 00:00:07,875 IT'S THE THIRD DAY OF THE EVENT. 3 00:00:07,875 --> 00:00:12,814 THIS MORNING WE HAVE THE GROUP 4 00:00:12,814 --> 00:00:23,358 FROM EMORY WITH THE P.I.s, MIRKO 5 00:00:23,725 --> 00:00:31,165 PAIARDINI AND ANDRES FINZI. 6 00:00:31,165 --> 00:00:36,838 >> THANK YOU, I'M HAPPY IT 7 00:00:36,838 --> 00:00:39,407 PRESENT THE COLLABORATORY AND IT 8 00:00:39,407 --> 00:00:41,075 INCLUDES 16 INSTITUTION FROM 9 00:00:41,075 --> 00:00:44,412 FIVE DIFFERENT COUNTRIES AND THE 10 00:00:44,412 --> 00:00:47,815 END OF YEAR THREE WE EXTENDED 11 00:00:47,815 --> 00:00:50,952 THE COLLABORATORY WITH U PEN. 12 00:00:50,952 --> 00:00:52,186 SO AN IMPORTANT GOAL IS THE 13 00:00:52,186 --> 00:00:55,123 TRAINING OF THE NEXT GENERATION 14 00:00:55,123 --> 00:00:57,392 OF HIV CURE SCIENTISTS. 15 00:00:57,392 --> 00:01:00,895 WE HAVE SCHOLARSHIP FOR HIV CURE 16 00:01:00,895 --> 00:01:02,230 RESEARCH WITH THE SUPPORT FROM 17 00:01:02,230 --> 00:01:04,132 THE EMORY SCHOOL OF MEDICINE AND 18 00:01:04,132 --> 00:01:06,334 FIFTH YEAR WAS AWARDED AND YOU 19 00:01:06,334 --> 00:01:07,702 SEE SOME OF THE WORK IN THE 20 00:01:07,702 --> 00:01:10,371 PRESENTATION AND WE HAVE THE 21 00:01:10,371 --> 00:01:15,643 SECOND ONE THE RFA JUST CAME 22 00:01:15,643 --> 00:01:18,012 OUT. 23 00:01:18,012 --> 00:01:23,151 AND THE INVESTIGATOR WORKED WITH 24 00:01:23,151 --> 00:01:24,886 HIV AS YOU CAN SEE. 25 00:01:24,886 --> 00:01:29,991 WE HAVE COMMUNITY OUTREACH AND 26 00:01:29,991 --> 00:01:31,759 ENGAGEMENT THANKS ONE THE 27 00:01:31,759 --> 00:01:33,061 COLLABORATION WITH SISTER LOVE 28 00:01:33,061 --> 00:01:40,068 AND WE HAVE BEEN INVOLVED IN 29 00:01:40,068 --> 00:01:43,204 POLICY SESSION AND WE HAVE AN 11 30 00:01:43,204 --> 00:01:46,341 WEEK INTERNSHIP PROGRAM FOR 31 00:01:46,341 --> 00:01:47,342 UNDERREPRESENTED MINORITY 32 00:01:47,342 --> 00:01:52,313 STUDENT AND HAVE BEEN INVOLVED 33 00:01:52,313 --> 00:01:55,049 IN THE COMMUNITY EVENT AND THE 34 00:01:55,049 --> 00:01:58,519 25th ANNIVERSARY AND ORGANIZED A 35 00:01:58,519 --> 00:02:02,090 COOK-OUT AND PARTICIPATED 36 00:02:02,090 --> 00:02:04,992 WORKING AND PRESENT OUR WORK 37 00:02:04,992 --> 00:02:09,497 BACK IN OCTOBER IN ATLANTA. 38 00:02:09,497 --> 00:02:15,503 AND I'D LIKE TO THANK SISTER 39 00:02:15,503 --> 00:02:17,238 LOVE WOMEN LIVING WITH HIV MORE 40 00:02:17,238 --> 00:02:19,006 THAN 20 YEARS. 41 00:02:19,006 --> 00:02:23,244 WE'VE ALSO BEEN SELECTED FOR THE 42 00:02:23,244 --> 00:02:24,412 WORK THAT'S BEEN SHOWN LAST 43 00:02:24,412 --> 00:02:27,715 MONTH IN OCTOBER IN LOS ANGELES 44 00:02:27,715 --> 00:02:30,385 THE CONFERENCE WITH MORE THAN 45 00:02:30,385 --> 00:02:31,252 12,000 ATTENDEES. 46 00:02:31,252 --> 00:02:36,624 THIS IS FOCUSSED ON COMMUNITY 47 00:02:36,624 --> 00:02:40,862 OUTREACH AND WE HAVE A VIDEO. 48 00:02:40,862 --> 00:02:42,497 WE ORGANIZED AN EVENT FOR THE 49 00:02:42,497 --> 00:02:45,299 WORLD AIDS DAY. 50 00:02:45,299 --> 00:02:47,668 A GALLERY SHOWCASE OF PEOPLE 51 00:02:47,668 --> 00:02:49,404 LIVING WITH HIV AND WE'LL SHARE 52 00:02:49,404 --> 00:02:52,173 THE RESEARCH AS PART OF THIS 53 00:02:52,173 --> 00:02:52,707 EVENT. 54 00:02:52,707 --> 00:02:56,944 WE'RE ALSO ORGANIZED AN EVENT IN 55 00:02:56,944 --> 00:02:59,680 EDUCATIONAL SYMPOSIUM IN SOUTH 56 00:02:59,680 --> 00:03:01,582 AFRICA. 57 00:03:01,582 --> 00:03:05,219 SO WITH THAT I'LL MOVE TO THE 58 00:03:05,219 --> 00:03:10,558 ROOM PART WE'VE PRESENTED MANY 59 00:03:10,558 --> 00:03:15,696 CONFERENCE AND HAVE 50 PUBLISHED 60 00:03:15,696 --> 00:03:16,030 PAPERS. 61 00:03:16,030 --> 00:03:18,132 WE ARE NOT COUNTING ALL THE 62 00:03:18,132 --> 00:03:21,302 PAPER FROM ALL THE 63 00:03:21,302 --> 00:03:22,236 COLLABORATORY. 64 00:03:22,236 --> 00:03:24,338 THEY'RE FULLY SUPPORTED ON THE 65 00:03:24,338 --> 00:03:28,309 PRIORITY OF HIV. 66 00:03:28,309 --> 00:03:30,445 PUBLISHED IN JOURNAL AND THE 67 00:03:30,445 --> 00:03:33,948 INDUCING LATENCY IN CELLS AND 68 00:03:33,948 --> 00:03:35,616 MECHANISMS HAPPENING. 69 00:03:35,616 --> 00:03:37,718 WE'VE BEEN DESCRIBING THE FUTURE 70 00:03:37,718 --> 00:03:43,825 WITH POST-TREATMENT CONTROL IN 71 00:03:43,825 --> 00:03:45,059 NONHUMAN PRIMATE AND VIRUS 72 00:03:45,059 --> 00:03:50,164 REPLICATION AND DOING 73 00:03:50,164 --> 00:03:53,401 INTERVENTION INCLUDING A STUDY 74 00:03:53,401 --> 00:03:54,602 CHARACTERIZED THE COMPOUND AND 75 00:03:54,602 --> 00:03:58,439 THE MECHANISM OF WORK AND 76 00:03:58,439 --> 00:04:01,309 BLOCKED INFECTION AND INCLUDING 77 00:04:01,309 --> 00:04:01,809 MACROPHAGES. 78 00:04:01,809 --> 00:04:06,380 AND I WANT TO NOTE ON CURING HIV 79 00:04:06,380 --> 00:04:10,651 I HELPED LEAD WITH A MULTIPLE 80 00:04:10,651 --> 00:04:13,287 MEMBERS COLLABORATORIES. 81 00:04:13,287 --> 00:04:15,289 I'LL TAKE A FEW MINUTES TO 82 00:04:15,289 --> 00:04:17,191 DESCRIBE A COUPLE STUDIES 83 00:04:17,191 --> 00:04:18,392 CONVENIENTLY. 84 00:04:18,392 --> 00:04:22,330 ESTABLISHED. 85 00:04:22,330 --> 00:04:25,132 ONE HAS BEEN CO-LED WITH MY LAB 86 00:04:25,132 --> 00:04:28,069 IDENTIFYING EARLY AND 87 00:04:28,069 --> 00:04:30,371 SIGNIFICANT EXPANSION OF TCF 88 00:04:30,371 --> 00:04:34,075 CELLS THAT MARK STIMULI AND ALSO 89 00:04:34,075 --> 00:04:36,043 MARKER OF DIFFERENTIATION LIKE 90 00:04:36,043 --> 00:04:36,577 CD 39. 91 00:04:36,577 --> 00:04:40,214 THE CELLS RESPOND AFTER 92 00:04:40,214 --> 00:04:43,885 INFECTION IN MACAQUES AND PEOPLE 93 00:04:43,885 --> 00:04:46,053 LIVING WITH HIV. 94 00:04:46,053 --> 00:04:48,990 WEAR SHORTED WITH BETTER CONTROL 95 00:04:48,990 --> 00:04:51,626 AND MORE OF THE CELLS AND 96 00:04:51,626 --> 00:04:54,795 MECHANISTICALLY WE FOUND THE 97 00:04:54,795 --> 00:04:57,298 CELLS EXPRESSED MORE THAN OTHER 98 00:04:57,298 --> 00:05:03,504 CELLS AND LOCALIZED IN CLOSE 99 00:05:03,504 --> 00:05:06,007 PROXIMITY TO THE CELLS AND IT'S. 100 00:05:06,007 --> 00:05:09,176 SELECTED FOR THE JOURNAL FOR 101 00:05:09,176 --> 00:05:09,677 RESEARCH BRIEFING. 102 00:05:09,677 --> 00:05:12,413 CONSISTENTLY A STUDY WITH 103 00:05:12,413 --> 00:05:13,314 COMMUNICATION THERE'S A 104 00:05:13,314 --> 00:05:14,749 DIFFERENT MODEL. 105 00:05:14,749 --> 00:05:16,284 NOW WE'LL TALK ABOUT POST 106 00:05:16,284 --> 00:05:18,586 TREATMENT CONTROL IN MACAQUES 107 00:05:18,586 --> 00:05:22,790 AND ONE OF THE KEY FEATURE OF 108 00:05:22,790 --> 00:05:26,761 CONTROL WAS THE PRESENCE OF 109 00:05:26,761 --> 00:05:28,563 CELLS AND THIS WAS AGAIN 110 00:05:28,563 --> 00:05:29,196 ASSOCIATED WITH EXPRESSION OF 111 00:05:29,196 --> 00:05:34,201 TCF1. 112 00:05:34,201 --> 00:05:36,837 I WANT TO HIGHLIGHT A PAPER THAT 113 00:05:36,837 --> 00:05:38,573 CAME OUT WEEKS AGO A 114 00:05:38,573 --> 00:05:43,811 COLLABORATION WITH OUR INDUSTRY 115 00:05:43,811 --> 00:05:47,782 PARTNER WHERE WE BROUGHT PD-1 IN 116 00:05:47,782 --> 00:05:50,384 MACAQUES AND FOUND A PROLONGED 117 00:05:50,384 --> 00:05:52,720 UP TO SIX MONTH CONTROL IN LARGE 118 00:05:52,720 --> 00:05:55,189 MAJORITY OF THE ANIMAL DURING 119 00:05:55,189 --> 00:05:58,059 THE TREATMENT IDENTIFIED AND WE 120 00:05:58,059 --> 00:06:00,928 STILL HAVE REMAINING CHALLENGES 121 00:06:00,928 --> 00:06:03,464 REGARDING THE SAFETY OF THE 122 00:06:03,464 --> 00:06:05,700 SYSTEM AND LONGEVITY OF THE 123 00:06:05,700 --> 00:06:05,967 RESPONSE. 124 00:06:05,967 --> 00:06:10,404 WE HAVE ANIMAL STUDY FOCUSSING 125 00:06:10,404 --> 00:06:12,607 ON THIS STUDY AND I CANNOT 126 00:06:12,607 --> 00:06:14,775 PRESENT THE DATA TODAY BUT SEEMS 127 00:06:14,775 --> 00:06:16,911 TO BE QUITE EXCITING. 128 00:06:16,911 --> 00:06:19,113 SO WITH THAT I'LL INTRODUCE THE 129 00:06:19,113 --> 00:06:19,380 SPEAKERS. 130 00:06:19,380 --> 00:06:21,649 A KEY PRIORITY FOR HIV IS 131 00:06:21,649 --> 00:06:26,253 UNDERSTANDING WHY INFECTED CELLS 132 00:06:26,253 --> 00:06:28,389 SURVIVE AND BECOME A RESERVOIR 133 00:06:28,389 --> 00:06:30,758 AND TRY TO TARGET THE MECHANISM 134 00:06:30,758 --> 00:06:34,428 AND WE'LL DESCRIBE ONE OF THESE 135 00:06:34,428 --> 00:06:37,665 MECHANISMS OF SURVIVAL AND THE 136 00:06:37,665 --> 00:06:41,102 CLOSE CONFIRMATION THE HIV HAVE 137 00:06:41,102 --> 00:06:44,405 TARGETING WITH COMPOUNDS. 138 00:06:44,405 --> 00:06:45,706 MEMBERS OF THE COLLABORATORY IS 139 00:06:45,706 --> 00:06:48,409 IDENTIFIED IN OTHER MECHANISMS 140 00:06:48,409 --> 00:06:52,279 OF SURVIVOR OF INFECTED CELLS 141 00:06:52,279 --> 00:06:56,017 AND WILL PRESENT HOW WE TARGET 142 00:06:56,017 --> 00:06:58,452 AND IMPACT PERSISTENCE IN 143 00:06:58,452 --> 00:07:01,622 NONHUMAN PRIMATES. 144 00:07:01,622 --> 00:07:03,591 NOT ONLY THE INFECTED CELLS WHY 145 00:07:03,591 --> 00:07:06,661 THEY SURVIVE BUT THE 146 00:07:06,661 --> 00:07:07,828 INTERACTION. 147 00:07:07,828 --> 00:07:10,164 AND WE'LL PRESENT ONE OF THE 148 00:07:10,164 --> 00:07:13,134 UNIQUE CONTRIBUTION FOR HIV AND 149 00:07:13,134 --> 00:07:16,604 THE ROLE OF CD 8 T CELLS AND 150 00:07:16,604 --> 00:07:20,241 PRESENT MECHANISTIC INSIGHT HOW 151 00:07:20,241 --> 00:07:21,475 THIS IS HAPPENING. 152 00:07:21,475 --> 00:07:24,311 AND DESCRIBE THE FEATURES OF THE 153 00:07:24,311 --> 00:07:28,082 CELLS BETTER ASSOCIATED 154 00:07:28,082 --> 00:07:33,954 INCLUDING THE ROLE OF IL10 AND 155 00:07:33,954 --> 00:07:37,324 PD 1 AND WE AND A REMAINING 156 00:07:37,324 --> 00:07:40,361 CHALLENGE IS THAT MANY CD 8 157 00:07:40,361 --> 00:07:44,131 CELLS DO NOT LOCALIZE TO THE 158 00:07:44,131 --> 00:07:45,466 TISSUE AND YOU'LL SEE 159 00:07:45,466 --> 00:07:48,936 PRESENTATION ON NEW STRATEGY 160 00:07:48,936 --> 00:07:54,475 BASED TO REDIRECT CELLS TO THE 161 00:07:54,475 --> 00:07:56,544 LYMPHOID TISSUE. 162 00:07:56,544 --> 00:07:59,814 WITH THAT I'LL HAVE ANDRES START 163 00:07:59,814 --> 00:08:00,781 HIS PRESENTATION. 164 00:08:00,781 --> 00:08:01,115 >> THANK YOU. 165 00:08:01,115 --> 00:08:03,851 I'M HAPPY TO BE HERE TO PRESENT 166 00:08:03,851 --> 00:08:05,920 THE WORK WE'RE DOING WITHIN THE 167 00:08:05,920 --> 00:08:07,121 HIV COLLABORATORY. 168 00:08:07,121 --> 00:08:09,690 OUR GOAL IS TO DEVELOP NEW 169 00:08:09,690 --> 00:08:11,158 STRATEGIES TO ELIMINATE INFECTED 170 00:08:11,158 --> 00:08:11,492 CELLS. 171 00:08:11,492 --> 00:08:14,628 WE LEARNED WE CAN DO THAT IF WE 172 00:08:14,628 --> 00:08:17,698 OPEN THE ENVELOPE LIKE A PROTEIN 173 00:08:17,698 --> 00:08:19,633 AT THE SURFACE AND GET TO THE 174 00:08:19,633 --> 00:08:21,936 INFECTED CELLS FOR THE CURE. 175 00:08:21,936 --> 00:08:23,704 WE HAVE SHOWN THE VIRUS DOES ALL 176 00:08:23,704 --> 00:08:27,475 IT CAN TO RENDER THE IMMUNE 177 00:08:27,475 --> 00:08:29,844 CELLS INVISIBLE TO THE IMMUNE 178 00:08:29,844 --> 00:08:31,979 SYSTEM AND ONE KEEPS THE 179 00:08:31,979 --> 00:08:34,315 ENVELOPE CLOSED AND THE 180 00:08:34,315 --> 00:08:36,450 ANTIBODIES PRESENT AND THOSE 181 00:08:36,450 --> 00:08:38,819 WITH HIV DO NOT RECOGNIZE AND 182 00:08:38,819 --> 00:08:43,157 THEREFORE OPEN IT UP BY USING 183 00:08:43,157 --> 00:08:46,794 MEMETICS AND THEY BEHAVE LIKE 184 00:08:46,794 --> 00:08:52,099 CD4 AND OPEN AT THE TRIMER AND 185 00:08:52,099 --> 00:08:54,201 RECOGNIZED BY ANTIBODIES AND CAN 186 00:08:54,201 --> 00:08:58,305 RECRUIT THE CELLS AND THESE ARE 187 00:08:58,305 --> 00:09:00,407 ELIMINATED BY THE DISEASE 188 00:09:00,407 --> 00:09:03,110 IT'S ALWAYS A BIT MORE 189 00:09:03,110 --> 00:09:03,944 COMPLICATED THAN IT LOOKS AND 190 00:09:03,944 --> 00:09:10,551 OPEN UP THE TRIMER ENOUGH TO THE 191 00:09:10,551 --> 00:09:12,253 ANTIBODIES SHOWN HERE IN BLACK 192 00:09:12,253 --> 00:09:14,221 GET ENGAGED AND AFTER THE 193 00:09:14,221 --> 00:09:16,824 BINDING IT FURTHER OPENS UP THE 194 00:09:16,824 --> 00:09:17,057 TRIMER. 195 00:09:17,057 --> 00:09:18,492 THERE'S A SEQUENTIAL OPENING OF 196 00:09:18,492 --> 00:09:22,396 THE TRIMER TO ENGAGE ANTIBODIES 197 00:09:22,396 --> 00:09:24,632 CALLED ANTI-CLUSTER ANTIBODIES. 198 00:09:24,632 --> 00:09:26,967 YOU HAVE THE MEMETICS AND YOU 199 00:09:26,967 --> 00:09:31,806 HAVE THIS COCKTAIL THE CELLS ARE 200 00:09:31,806 --> 00:09:33,007 ELIMINATED EFFICIENTLY AND IF 201 00:09:33,007 --> 00:09:35,709 YOU PUT THIS IN HUMANIZED MICE 202 00:09:35,709 --> 00:09:37,378 YOU HAVE A SIGNIFICANT DELAY IN 203 00:09:37,378 --> 00:09:39,480 VIRAL REBOUND AND DECREASE IN 204 00:09:39,480 --> 00:09:40,948 THE SIZE OF THE VIRAL RESERVOIR. 205 00:09:40,948 --> 00:09:42,616 THE QUESTION IS CAN WE DO 206 00:09:42,616 --> 00:09:43,384 BETTER? 207 00:09:43,384 --> 00:09:45,519 WE ARE OBSESSED WITH IMPROVING 208 00:09:45,519 --> 00:09:47,588 THE POTENCY OF THE COCKTAIL. 209 00:09:47,588 --> 00:09:53,594 ONE WAY IS TO IMPROVE THE 210 00:09:53,594 --> 00:09:59,867 MEMETIC AND THIS IS WHAT THEY'RE 211 00:09:59,867 --> 00:10:04,905 DOING. 212 00:10:04,905 --> 00:10:08,008 AND. 213 00:10:08,008 --> 00:10:13,013 THE DERIVATIVE WHICH IS MORE 214 00:10:13,013 --> 00:10:14,481 POTENT AND MORE EFFICIENT WITH 215 00:10:14,481 --> 00:10:18,385 THE COMBINATION OF ANTIBODIES OR 216 00:10:18,385 --> 00:10:21,355 IN PLASMA OF PEOPLE LIVING WITH 217 00:10:21,355 --> 00:10:21,522 HIV. 218 00:10:21,522 --> 00:10:24,258 AND HOW DOES IT WORK IN HUMAN 219 00:10:24,258 --> 00:10:28,095 MICE WITH THE MEMETICS AND THIS 220 00:10:28,095 --> 00:10:31,332 IS WHAT YALE HAS BEEN DOING WITH 221 00:10:31,332 --> 00:10:36,403 HUMANIZED MICE SUPPORTING 222 00:10:36,403 --> 00:10:37,571 FUNCTION. 223 00:10:37,571 --> 00:10:48,115 AND THEY NEED THE ANTIBODIES AS 224 00:10:53,187 --> 00:10:54,388 THE CONTROL. 225 00:10:54,388 --> 00:10:57,124 AND THIS PROVIDES THE 226 00:10:57,124 --> 00:10:58,392 ANTIBODIES. 227 00:10:58,392 --> 00:11:03,530 WE'RE PROVIDING AT THE TIME AND 228 00:11:03,530 --> 00:11:05,332 MANY TOGETHER WITH ANTIBODIES 229 00:11:05,332 --> 00:11:08,402 AND EVERY SINGLE ANIMAL SO IT'S 230 00:11:08,402 --> 00:11:10,671 ONE INDIVIDUAL ANIMAL AND YOU 231 00:11:10,671 --> 00:11:12,239 HAVE AROUND A FOUR WEEK DELAY IN 232 00:11:12,239 --> 00:11:13,540 VIRAL REBOUND. 233 00:11:13,540 --> 00:11:15,276 BUT WHAT WAS REALLY INTERESTED 234 00:11:15,276 --> 00:11:18,746 IS WHEN YOU PROVIDE THE MEMETIC 235 00:11:18,746 --> 00:11:23,083 COCKTAIL AT THE TIME OF ART 236 00:11:23,083 --> 00:11:24,785 INITIATION YOU HAVE THREE TO 237 00:11:24,785 --> 00:11:26,687 FIVE WEEKS ON DELAY OF VIRAL 238 00:11:26,687 --> 00:11:28,555 REBOUND BUT IN FIVE ANIMALS YOU 239 00:11:28,555 --> 00:11:29,490 SEE VIRAL CONTROL. 240 00:11:29,490 --> 00:11:30,724 YOU ONLY SEE BLIPS. 241 00:11:30,724 --> 00:11:33,794 IF YOU PUT IT TOGETHER IN THE 242 00:11:33,794 --> 00:11:35,763 CONTROL ANIMALS VIRAL REBOUNDS 243 00:11:35,763 --> 00:11:36,664 IMMEDIATELY AROUND FOUR WEEKS 244 00:11:36,664 --> 00:11:38,299 DELAY IF YOU PROVIDER AT THE 245 00:11:38,299 --> 00:11:43,971 TIME OF ART AND ACTUALLY HAVE 246 00:11:43,971 --> 00:11:46,407 CONTROL WITH BLIPS IF YOU 247 00:11:46,407 --> 00:11:47,841 PROVIDE AT THE TIME OF ART 248 00:11:47,841 --> 00:11:50,544 INITIATION AND THIS IS 249 00:11:50,544 --> 00:11:54,048 ASSOCIATED WITH DECREASING THE 250 00:11:54,048 --> 00:11:57,484 SIZE OF THE VIRAL RESERVOIR AND 251 00:11:57,484 --> 00:11:58,953 THE MEMETICS ALONE AND THE 252 00:11:58,953 --> 00:12:00,321 DECREASE WHERE YOU PUT IT 253 00:12:00,321 --> 00:12:01,855 TOGETHER WITH ANTIBODIES AND 254 00:12:01,855 --> 00:12:02,923 PARTICULARLY POTENT IF YOU DO IT 255 00:12:02,923 --> 00:12:05,059 AT THE TIME OF ART INITIATION. 256 00:12:05,059 --> 00:12:07,494 THE QUESTION IS CAN WE DO 257 00:12:07,494 --> 00:12:07,728 BETTER? 258 00:12:07,728 --> 00:12:10,698 CAN WE KEEP IMPROVING THE 259 00:12:10,698 --> 00:12:11,265 COCKTAIL? 260 00:12:11,265 --> 00:12:13,734 OF COURSE WE CAN HAVE MORE 261 00:12:13,734 --> 00:12:16,070 POTENT MEMETICS BUT CAN IMPROVE 262 00:12:16,070 --> 00:12:18,238 THE ANTIBODY CONTENT OF THE 263 00:12:18,238 --> 00:12:20,074 COCKTAIL. 264 00:12:20,074 --> 00:12:22,710 AND WE'RE SAYING THAT BECAUSE 265 00:12:22,710 --> 00:12:24,778 ALEXANDRA HAS BEEN LOOKING AT 266 00:12:24,778 --> 00:12:26,313 PLASMA WITH PEOPLE WITH HIV AND 267 00:12:26,313 --> 00:12:27,815 YOU HAVE 50 DIFFERENT 268 00:12:27,815 --> 00:12:28,816 INDIVIDUALS LIVING WITH HIV AND 269 00:12:28,816 --> 00:12:35,089 SEE IN ALL THE CASES WHETHER WE 270 00:12:35,089 --> 00:12:38,025 HAVE THIS YOU GET OTHER 271 00:12:38,025 --> 00:12:39,059 RECOGNITION BUT YOU CAN 272 00:12:39,059 --> 00:12:40,894 APPRECIATE AND WANTED TO 273 00:12:40,894 --> 00:12:44,264 UNDERSTAND WHY SOME PLASMA WAS 274 00:12:44,264 --> 00:12:46,533 SUPERIOR THAN OTHERS IN THE 275 00:12:46,533 --> 00:12:49,103 PRESENCE OF THE MEMETIC AND WE 276 00:12:49,103 --> 00:12:51,338 WERE MISSING ONE FAMILY RESPONSE 277 00:12:51,338 --> 00:12:56,176 AND WE MADE A COCKTAIL OF THAT. 278 00:12:56,176 --> 00:13:00,147 WE WERE MISSING THE CLUSTER 1 279 00:13:00,147 --> 00:13:00,514 REGION. 280 00:13:00,514 --> 00:13:02,783 IN GRAY YOU CAN SEE IF YOU 281 00:13:02,783 --> 00:13:04,318 PROVIDE THE TWO OR THREE 282 00:13:04,318 --> 00:13:06,053 ANTIBODIES THERE'S NO MEMETIC IT 283 00:13:06,053 --> 00:13:07,521 DOESN'T HAPPEN. 284 00:13:07,521 --> 00:13:09,156 BUT IF YOU PROVIDE THE MEMETIC 285 00:13:09,156 --> 00:13:11,859 IN BLUE IT GOES UP WITH EVERY 286 00:13:11,859 --> 00:13:13,627 VIRUS WE TESTED AND THE 287 00:13:13,627 --> 00:13:14,828 COMBINATION OF THREE ANTIBODIES 288 00:13:14,828 --> 00:13:15,729 IS SUPERIOR. 289 00:13:15,729 --> 00:13:18,432 THIS IS SUPERIOR TO EVERYONE WE 290 00:13:18,432 --> 00:13:18,866 COMPARED. 291 00:13:18,866 --> 00:13:22,403 THIS IS ACTIVITY AGAIN EVERY 292 00:13:22,403 --> 00:13:26,373 COMBINATION OF BNAB AND SO FAR 293 00:13:26,373 --> 00:13:28,108 THE COCKTAIL WE HAVE IS THE MOST 294 00:13:28,108 --> 00:13:29,076 POTENT WE HAVE. 295 00:13:29,076 --> 00:13:33,814 CAN WE DO BETTER? 296 00:13:33,814 --> 00:13:35,816 SO ON TOP OF OF TRYING TO MAKE A 297 00:13:35,816 --> 00:13:37,885 MORE POTENT COCKTAIL WE CAN HAVE 298 00:13:37,885 --> 00:13:45,092 THE INFECTED CELLS TO ADDC. 299 00:13:45,092 --> 00:13:48,962 AND WE HAVE DATA AND THIS WILL 300 00:13:48,962 --> 00:13:51,632 GO UP AND OF COURSE WE STILL 301 00:13:51,632 --> 00:13:53,033 HAVE A BIT MORE ENVELOPE SO YOU 302 00:13:53,033 --> 00:13:55,335 HAVE MORE TARGET FOR THE 303 00:13:55,335 --> 00:13:55,636 MEMETIC. 304 00:13:55,636 --> 00:13:58,639 IF YOU USE PLASMA FROM 305 00:13:58,639 --> 00:13:59,440 UNINFECTED INDIVIDUAL NO 306 00:13:59,440 --> 00:14:01,508 RECOGNITION OF THE INFECTED CELL 307 00:14:01,508 --> 00:14:04,044 AND PEOPLE WITH HIV YOU GET 308 00:14:04,044 --> 00:14:06,246 RECOGNITION AND IN BLUE THE 309 00:14:06,246 --> 00:14:09,550 RECOGNITION GOES HIGH AND EVEN 310 00:14:09,550 --> 00:14:11,518 HIGHER WHEN YOU ADD BETA TO THE 311 00:14:11,518 --> 00:14:13,954 TARGET AND TRUE WHEN YOU DO THE 312 00:14:13,954 --> 00:14:16,356 COMBINATION COCKTAIL OF 313 00:14:16,356 --> 00:14:16,757 ANTIBODIES. 314 00:14:16,757 --> 00:14:18,926 AND THAT'S TRANSLATED TO ADCC. 315 00:14:18,926 --> 00:14:24,164 WE HAVE ENHANCED WHEN WE COMBINE 316 00:14:24,164 --> 00:14:27,134 AND THIS IS ALSO DUE WHEN YOU 317 00:14:27,134 --> 00:14:29,670 HAVE DATA SOME LIGANDS GET 318 00:14:29,670 --> 00:14:32,773 REGULATED SO THE INFECTED CELL 319 00:14:32,773 --> 00:14:34,675 BECOMES MORE SUSCEPTIBLE TO 320 00:14:34,675 --> 00:14:34,908 KILLING. 321 00:14:34,908 --> 00:14:36,310 SOMETHING I LIKE ABOUT THIS IS 322 00:14:36,310 --> 00:14:38,879 WE GO FROM IN VITRO TO EX VIVO. 323 00:14:38,879 --> 00:14:41,915 WE HUMANIZE MICE AND NONHUMAN 324 00:14:41,915 --> 00:14:47,321 PRIMATES HAVE A TIR -- CIRCLE 325 00:14:47,321 --> 00:14:50,824 AND HOW'S IT LOOK IN NONHUMAN 326 00:14:50,824 --> 00:14:51,959 PRIMATES? 327 00:14:51,959 --> 00:14:57,030 AND THIS IS PREVIOUS COMBINATION 328 00:14:57,030 --> 00:14:57,965 TOGETHER AND WE'LL HAVE TWO 329 00:14:57,965 --> 00:15:05,005 GROUPS OF ANIMALS AND PROVIDE 330 00:15:05,005 --> 00:15:07,508 THE COCKTAIL AT TIME OF ART 331 00:15:07,508 --> 00:15:08,675 INITIATION AND THIS IS WHERE WE 332 00:15:08,675 --> 00:15:09,376 ARE SO FAR. 333 00:15:09,376 --> 00:15:12,546 THE STUDY IS ONGOING. 334 00:15:12,546 --> 00:15:13,981 IT'S NOT COMPLETE. 335 00:15:13,981 --> 00:15:15,549 WHEN YOU PROVIDE THE ANTIBODIES 336 00:15:15,549 --> 00:15:21,355 ALONE AT THE TIME OF ART 337 00:15:21,355 --> 00:15:26,193 INITIATION IT DOESN'T HAPPEN BUT 338 00:15:26,193 --> 00:15:28,095 WITH MEMETIC YOU GET MORE OF A 339 00:15:28,095 --> 00:15:31,365 VIRAL LOAD AND WANT TO KNOW IF 340 00:15:31,365 --> 00:15:33,000 IT AFFECT THE SIZE OF THE 341 00:15:33,000 --> 00:15:34,568 RESERVOIR THE ANIMAL WILL BE 342 00:15:34,568 --> 00:15:36,837 TREATED AND WE'LL WAIT FOR TIME 343 00:15:36,837 --> 00:15:42,376 TO VIRAL REBOUND AND MAKE SURE 344 00:15:42,376 --> 00:15:45,279 THERE'S RESERVOIR. 345 00:15:45,279 --> 00:15:47,681 WE HAVE THE AMOUNT TO THE 346 00:15:47,681 --> 00:15:48,982 NONHUMAN PRIMATES AND I'D LIKE 347 00:15:48,982 --> 00:15:50,617 TO THANK MY LAB AND 348 00:15:50,617 --> 00:15:51,251 COLLABORATORS AND PARTICIPANTS 349 00:15:51,251 --> 00:16:01,595 AND YOUR ATTENTION. 350 00:16:07,334 --> 00:16:08,168 >> GOOD MORNING, EVERYONE. 351 00:16:08,168 --> 00:16:12,172 IT'S GREAT TO BE HERE. 352 00:16:12,172 --> 00:16:18,579 THANKS FOR ORGANIZING THIS AND 353 00:16:18,579 --> 00:16:20,080 NIH COLLEAGUES. 354 00:16:20,080 --> 00:16:29,856 IT WAS 10 YEARS AGO THAT I WAS 355 00:16:29,856 --> 00:16:40,467 SITTING WITH ANDREW BAD LY 356 00:16:41,902 --> 00:16:42,369 [AUDIO DIGITIZING] 357 00:16:42,369 --> 00:16:47,641 AND WE WERE TALKING ABOUT 358 00:16:47,641 --> 00:16:50,377 POTENTIAL BE NEW IDEAS TO CURE 359 00:16:50,377 --> 00:16:53,680 HIV INFECTION AND THEY SAID, 360 00:16:53,680 --> 00:16:55,082 GUIDO WE SHOULD TARGET WAYS TO 361 00:16:55,082 --> 00:16:57,150 GET THE CELLS TO DIE OF 362 00:16:57,150 --> 00:16:58,452 APOPTOSIS AND NOT JUST THE SHOCK 363 00:16:58,452 --> 00:16:59,453 AND KILL. 364 00:16:59,453 --> 00:17:00,954 WE EXPECT THE IMMUNE SYSTEM TO 365 00:17:00,954 --> 00:17:06,226 COME IN AND DO THE JOB ONCE THE 366 00:17:06,226 --> 00:17:10,631 VIRUS HAS BEEN REACTIVATED AND 367 00:17:10,631 --> 00:17:13,133 WE INVENT THE MONIKER SHOCK AND 368 00:17:13,133 --> 00:17:15,269 SUICIDE AND WERE TOLD IT'S 369 00:17:15,269 --> 00:17:16,303 PROBABLY NOT GOOD LANGUAGE. 370 00:17:16,303 --> 00:17:21,241 I THINK THE CONCEPT IS THERE. 371 00:17:21,241 --> 00:17:24,144 AND IT'S NICE TO SEE YEARS LATER 372 00:17:24,144 --> 00:17:27,714 ALMOST 10 YEARS LATER TO SEE 373 00:17:27,714 --> 00:17:30,284 THE CONCEPT TAKING OFF. 374 00:17:30,284 --> 00:17:32,886 FOR OUR COMMUNITY THE GOAL OF 375 00:17:32,886 --> 00:17:35,989 THE STUDY WAS BLOCKING MOLECULES 376 00:17:35,989 --> 00:17:39,226 HELPING INFECTED CD4 T CELLS TO 377 00:17:39,226 --> 00:17:40,327 SURVIVE LEADING TO THE 378 00:17:40,327 --> 00:17:45,265 ELIMINATION OF THE RESERVOIR. 379 00:17:45,265 --> 00:17:46,833 WE'RE USING A PARTICULAR DRUG 380 00:17:46,833 --> 00:17:49,136 AND PROMOTE CELL DEATH IN 381 00:17:49,136 --> 00:17:50,237 INFECTED CELLS AND WHAT WE ARE 382 00:17:50,237 --> 00:17:51,838 LEARNING IS WE CAN DO 383 00:17:51,838 --> 00:17:54,775 EXPERIMENTS IN NONHUMAN PRIMATES 384 00:17:54,775 --> 00:17:56,877 AND ASSESSING HOW THIS DRUG 385 00:17:56,877 --> 00:17:58,679 IMPACT ON THE ESTABLISHMENT AND 386 00:17:58,679 --> 00:18:00,213 MAINTENANCE OF THE RESERVOIR BUT 387 00:18:00,213 --> 00:18:04,017 IN THE SETTING OF EARLIER 388 00:18:04,017 --> 00:18:08,255 INITIATION OR CHRONIC ART AND 389 00:18:08,255 --> 00:18:08,822 WHY IT'S IMPORTANT. 390 00:18:08,822 --> 00:18:11,091 A REASONABLE APPROACH TO CURE 391 00:18:11,091 --> 00:18:12,626 HIV INFECTION WILL INVOLVE 392 00:18:12,626 --> 00:18:15,629 REDUCING THE RESERVOIR OF CELLS 393 00:18:15,629 --> 00:18:17,431 WITH REPLICATION OF THE VIRUS 394 00:18:17,431 --> 00:18:22,269 THAT PERSISTS UNDER ART. 395 00:18:22,269 --> 00:18:24,871 SO, WHAT ANDY AND I DISCUSSED 396 00:18:24,871 --> 00:18:27,341 DURING THAT MEETING IT WAS. 397 00:18:27,341 --> 00:18:30,043 ING APPARENT WE'VE KNOWN FOR EYE 398 00:18:30,043 --> 00:18:31,111 LONG TIME I THINK THERE'S 399 00:18:31,111 --> 00:18:34,614 HUNDREDS OF PAPERS SHOWING 400 00:18:34,614 --> 00:18:38,118 SURVIVAL OF LYMPHOCYTES IS 401 00:18:38,118 --> 00:18:40,721 RELATED TO CHRONIC ABILITY TO 402 00:18:40,721 --> 00:18:43,857 BLOCK THE MITOCHONDRIAL 403 00:18:43,857 --> 00:18:47,694 APOPTOSIS THAT REALIZE ON CAS 9 404 00:18:47,694 --> 00:18:53,700 AND OTHERS AND AT THAT TIME IT 405 00:18:53,700 --> 00:18:55,168 BIOMEDICAL CLEAR THAT WE COULD 406 00:18:55,168 --> 00:19:03,710 GO IN THAT DIRECTION AND HIGH 407 00:19:03,710 --> 00:19:06,179 POSSIBLE -- HYPOTHESIZED WE 408 00:19:06,179 --> 00:19:11,184 COULD PUSH THE APOPTOSIS OF 409 00:19:11,184 --> 00:19:16,656 CELLS AND WE THOUGHT IT WAS 410 00:19:16,656 --> 00:19:25,198 SPECIFIC ENOUGH TO GIVE IT A TRY 411 00:19:25,198 --> 00:19:28,935 AND THERE WAS A STUDY OF CHRONIC 412 00:19:28,935 --> 00:19:31,338 LEUKEMIA AND THERAPY FOR THAT 413 00:19:31,338 --> 00:19:35,876 TYPE THAT HAD BEEN IN CLINICAL 414 00:19:35,876 --> 00:19:38,678 TRIALS AND WHAT WE DECIDED TO DO 415 00:19:38,678 --> 00:19:40,781 WAS TO SEE IF THIS BEAUTIFUL 416 00:19:40,781 --> 00:19:43,717 CONCEPT BLOCK THIS AND REMOVING 417 00:19:43,717 --> 00:19:51,158 THE BCL2 BLOCK EFFECTIVELY STOPS 418 00:19:51,158 --> 00:19:53,593 THE MITOCHONDRIAL PATHWAY OF 419 00:19:53,593 --> 00:19:58,098 APOPTOSIS AND GETTING RID OF THE 420 00:19:58,098 --> 00:20:00,167 INFECTED CELLS IN THE STUDY OF 421 00:20:00,167 --> 00:20:02,269 ART AND THOSE ARE THE TWO 422 00:20:02,269 --> 00:20:08,175 STUDIES THAT HAVE EXPLORED THE 423 00:20:08,175 --> 00:20:10,977 CONCEPT ONE WAS EXPLORED IN THE 424 00:20:10,977 --> 00:20:13,046 HUMANIZED MOUSE MODEL AND DOING 425 00:20:13,046 --> 00:20:14,414 RELATED WORK IN THE NONHUMAN 426 00:20:14,414 --> 00:20:17,117 PRIMATE MODEL. 427 00:20:17,117 --> 00:20:25,425 SO THIS IS THE FIRST STUDY BY 428 00:20:25,425 --> 00:20:26,393 THOMAS IN THE BACK OF THE ROOM 429 00:20:26,393 --> 00:20:29,129 AND IT WAS GIVEN TO MONKEYS 430 00:20:29,129 --> 00:20:36,169 DURING EARLY ART AND YOU SEE THE 431 00:20:36,169 --> 00:20:36,470 SCHEMATIC. 432 00:20:36,470 --> 00:20:44,578 AND THERE'S A GROUP OF ANIMALS 433 00:20:44,578 --> 00:20:47,747 AND ANOTHER GROUP GIVEN IT IN 434 00:20:47,747 --> 00:20:53,053 THE DEPLETION AND THE CD 8 435 00:20:53,053 --> 00:20:54,354 DEPLETION LEADS TO A MORE 436 00:20:54,354 --> 00:20:58,225 LATENCY ENVIRONMENT IN THE CD4 T 437 00:20:58,225 --> 00:21:00,126 CELLS AND IT'S EXCITING TO SEE 438 00:21:00,126 --> 00:21:02,162 THE MECHANISM DECIPHERED FOR 439 00:21:02,162 --> 00:21:03,597 THAT EFFECT. 440 00:21:03,597 --> 00:21:09,135 SO THIS IS BY DESIGN. 441 00:21:09,135 --> 00:21:11,838 I'D BE HAPPY TO ANSWER DETAILS 442 00:21:11,838 --> 00:21:12,973 IN THE DISCUSSION. 443 00:21:12,973 --> 00:21:16,510 AND CLEARLY THERE'S AN IMPORTANT 444 00:21:16,510 --> 00:21:20,881 IMMUNOLOGIC RESPONSE OF THE AND 445 00:21:20,881 --> 00:21:22,182 WE'VE SEEN THAT IN THE NEXT 446 00:21:22,182 --> 00:21:26,386 STUDY THERE'S A DEPLETION OF CD4 447 00:21:26,386 --> 00:21:32,859 CELLS AND THERE IS A GENERAL 448 00:21:32,859 --> 00:21:35,428 PERTURBATION OF THE DYNAMIC OF 449 00:21:35,428 --> 00:21:36,830 EXPRESSION YOU SEE REFLECTED ON 450 00:21:36,830 --> 00:21:42,736 THE RIGHT SIDE BY MEASURING 451 00:21:42,736 --> 00:21:47,474 EXPRESSION BY FLOW CYTOMETRY AND 452 00:21:47,474 --> 00:21:51,945 YOU SEE THE BIOLOGICAL READOUTS 453 00:21:51,945 --> 00:21:53,680 AND ONE IS THE CURB OF VIRAL 454 00:21:53,680 --> 00:22:00,687 LOAD DECLINE OF ANTIVIRAL 455 00:22:00,687 --> 00:22:02,589 THERAPY. 456 00:22:02,589 --> 00:22:06,960 AND SOME OF US HERE IN THE ROOM 457 00:22:06,960 --> 00:22:08,929 WEREN'T AROUND AT THIS TIME BUT 458 00:22:08,929 --> 00:22:11,097 THE MODEL STILL STANDS BUT YOU 459 00:22:11,097 --> 00:22:15,835 SEE THE COMBINATION OF CD 8 460 00:22:15,835 --> 00:22:18,672 DEPLETION AND IT ALONE SEEMS TO 461 00:22:18,672 --> 00:22:21,207 PERTURB THE SLOPE OF THE DECLINE 462 00:22:21,207 --> 00:22:23,910 OF VIREMIA SUGGESTING A 463 00:22:23,910 --> 00:22:29,115 DECREASED REDUCTION OF VIRUS OR 464 00:22:29,115 --> 00:22:30,850 INFECTED CELLS AND WE CAN GO TO 465 00:22:30,850 --> 00:22:32,519 THAT DURING THE DISCUSSION. 466 00:22:32,519 --> 00:22:34,788 IT'S A COMPLEX OBSERVATION THAT 467 00:22:34,788 --> 00:22:36,089 WOULD REQUIRE MORE THAN THE TIME 468 00:22:36,089 --> 00:22:39,159 I'M ALLOTTED TODAY. 469 00:22:39,159 --> 00:22:40,560 BUT IN TERMS OF THE RESERVOIR 470 00:22:40,560 --> 00:22:42,228 WHAT'S IMPORTANT TO NOTE IS WHEN 471 00:22:42,228 --> 00:22:47,767 YOU LOOK AT THE KINETIC OVER 472 00:22:47,767 --> 00:22:53,940 TIME OF BOTH THE CELLS 473 00:22:53,940 --> 00:22:56,576 EXPRESSING SHOWING INTEGRATED 474 00:22:56,576 --> 00:22:58,612 DNA EITHER BY TOTAL COUNT OR 475 00:22:58,612 --> 00:23:06,119 IPDA OR THE CELLS THAT ARE 476 00:23:06,119 --> 00:23:13,760 EXPRESSING INFECTED WITH SIV DNA 477 00:23:13,760 --> 00:23:17,130 EITHER AS A FRACTION OF THE CD4 478 00:23:17,130 --> 00:23:20,800 CELLS OR THE ABSOLUTE COPIES OF 479 00:23:20,800 --> 00:23:21,835 VIRUS PER ML BLOT. 480 00:23:21,835 --> 00:23:23,703 DIFFERENT WAYS OF LOOKING AT THE 481 00:23:23,703 --> 00:23:25,505 SAME PHENOMENON. 482 00:23:25,505 --> 00:23:26,840 THERE'S A SIGNIFICANT DECLINE 483 00:23:26,840 --> 00:23:29,709 YOU SEE THE LINES IN ORANGE AND 484 00:23:29,709 --> 00:23:29,909 BLACK. 485 00:23:29,909 --> 00:23:32,545 SIGNIFICANT FASTER DECLINE NA 486 00:23:32,545 --> 00:23:33,380 PERSISTS OVER TIME OF THE 487 00:23:33,380 --> 00:23:36,249 RESERVOIR IN THE ANIMAL TREATED 488 00:23:36,249 --> 00:23:38,985 WITH IT ALONE OR WITH CD 8 489 00:23:38,985 --> 00:23:39,786 DEPLETION COMPARED TO THE 490 00:23:39,786 --> 00:23:41,721 CONTROL LINES WHICH IS THE BLUE. 491 00:23:41,721 --> 00:23:45,692 AND THAT'S THE MAIN MESSAGE OF 492 00:23:45,692 --> 00:23:46,726 THIS PARTICULAR EXPERIMENT THAT 493 00:23:46,726 --> 00:23:47,627 AGAIN WE CAN DISCUSS MORE DURING 494 00:23:47,627 --> 00:23:50,096 THE DISCUSSION. 495 00:23:50,096 --> 00:23:59,139 THEN THE NEXT STUDY WAS TO TRY 496 00:23:59,139 --> 00:24:02,142 IT UP COMBINATION WITH A LATENCY 497 00:24:02,142 --> 00:24:06,346 APPROACH THE COMBINATION OF CD 8 498 00:24:06,346 --> 00:24:09,949 DEPLETION AND IL15 SUPER AGONIST 499 00:24:09,949 --> 00:24:15,689 AND A COCKTAIL OF SIV SPECIFIC 500 00:24:15,689 --> 00:24:16,690 NEUTRALIZING ANTIBODIES. 501 00:24:16,690 --> 00:24:19,125 THE IDEA IS TO SEE WHAT IT WOULD 502 00:24:19,125 --> 00:24:20,927 DO IN THE SETTING OF ESTABLISHED 503 00:24:20,927 --> 00:24:21,795 ART. 504 00:24:21,795 --> 00:24:26,132 THESE ARE ANIMALS TREATED FOR 505 00:24:26,132 --> 00:24:28,168 TWO YEARS WITH ANTIRETROVIRAL A 506 00:24:28,168 --> 00:24:30,537 REAL SUPPRESSION IN HIV INFECTED 507 00:24:30,537 --> 00:24:32,939 INDIVIDUALS OR PEOPLE LIVING 508 00:24:32,939 --> 00:24:37,310 WITH HIV AND TREATED WITH ART. 509 00:24:37,310 --> 00:24:40,180 THE RESULTS OF THE STUDY IS THAT 510 00:24:40,180 --> 00:24:42,849 WHILE WE CONFIRM THE ABILITY OF 511 00:24:42,849 --> 00:24:46,286 THE TREATMENT TO EXTRAPOLATE AND 512 00:24:46,286 --> 00:24:48,755 SEE THE THREE LINES IN ORANGE, 513 00:24:48,755 --> 00:24:51,191 PURPLE AND GREEN AND THE 514 00:24:51,191 --> 00:24:53,126 CONTROLS IN TERMS OF VIRUS 515 00:24:53,126 --> 00:24:54,994 REACTIVATION AND THE ART BUT ON 516 00:24:54,994 --> 00:24:57,831 THE RIGHT THE DNA COPIES PER 517 00:24:57,831 --> 00:24:59,733 MILLION CD4 CELLS AND THERE'S A 518 00:24:59,733 --> 00:25:02,802 HIGHLY SIGNIFICANT DECLINE AT 519 00:25:02,802 --> 00:25:04,104 DAY 56 POST TREATMENT IN THE 520 00:25:04,104 --> 00:25:06,639 GROUP OF ANIMALS THAT RECEIVED 521 00:25:06,639 --> 00:25:06,840 THIS. 522 00:25:06,840 --> 00:25:10,610 THERE'S A CONVERGENCE OF RESULTS 523 00:25:10,610 --> 00:25:14,214 AND THOSE ARE THE MAIN 524 00:25:14,214 --> 00:25:17,150 CONVERGENCE OF THE STUDY WHEN 525 00:25:17,150 --> 00:25:27,694 IT'S GIVEN AT THE BEGINNING OF 526 00:25:28,728 --> 00:25:31,097 ANTIVIRAL THERAPY AND THE 527 00:25:31,097 --> 00:25:34,334 INHIBITION OF IL2 IS SUFFICIENT 528 00:25:34,334 --> 00:25:37,036 TO PRODUCE AN INSTABILITY OF THE 529 00:25:37,036 --> 00:25:38,938 RESERVOIR THAT TRANSLATES TO 530 00:25:38,938 --> 00:25:44,010 LOWER LEVELS OF CELLS LAR HAVING 531 00:25:44,010 --> 00:25:45,044 THE VIRUS OVER TIME. 532 00:25:45,044 --> 00:25:46,446 I ACKNOWLEDGE THE FOLKS THAT 533 00:25:46,446 --> 00:25:52,051 HAVE DONE THE WORK AND I'LL GIVE 534 00:25:52,051 --> 00:26:02,195 IT BACK. 535 00:26:25,451 --> 00:26:28,288 AND WE HAVE A NATURAL FUNCTION 536 00:26:28,288 --> 00:26:31,124 THAT CAN INTERFERE WITH LRA 537 00:26:31,124 --> 00:26:33,660 ACTIVE IN VIVO. 538 00:26:33,660 --> 00:26:35,862 BY UNDERSTANDING HOW AND WHY 539 00:26:35,862 --> 00:26:36,996 THEY CAN ACTIVATE ACTIVITY IT 540 00:26:36,996 --> 00:26:38,731 CAN GIVE US THE ABILITY TO 541 00:26:38,731 --> 00:26:40,166 DESIGN MORE EFFECTIVE 542 00:26:40,166 --> 00:26:41,935 INTERVENTIONS WE CAN THEN USE 543 00:26:41,935 --> 00:26:47,373 FOR HIV SHOCK AND KILL CURE 544 00:26:47,373 --> 00:26:49,242 STRATEGIES. 545 00:26:49,242 --> 00:26:59,786 IT'S BEEN WELL AND NOW THERE'S 546 00:27:00,987 --> 00:27:02,555 EVIDENCE THEY HAVE A ROLE IN THE 547 00:27:02,555 --> 00:27:04,824 CONTROL OF VIRAL REPLICATION. 548 00:27:04,824 --> 00:27:08,761 THAT OF A NON-ANTIGEN SPECIFIC 549 00:27:08,761 --> 00:27:10,263 ROW LATENCY MECHANISM. 550 00:27:10,263 --> 00:27:15,034 THE NON CYTOLYTIC FUNCTIONS OF 551 00:27:15,034 --> 00:27:17,170 CELLS CAN ACT SYNERGISTICALLY IN 552 00:27:17,170 --> 00:27:18,638 THE ABSENCE OF ART. 553 00:27:18,638 --> 00:27:23,142 SO ON ONE SIDE YOU HAVE THE 554 00:27:23,142 --> 00:27:26,412 TARGETING OF PRODUCTIVELY 555 00:27:26,412 --> 00:27:27,680 INFECTED CD4 T CELLS TO TARGET 556 00:27:27,680 --> 00:27:30,350 FOR ELIMINATION AND ON THE OTHER 557 00:27:30,350 --> 00:27:32,919 SIDE YOU HAVE A VIRAL SILENCE 558 00:27:32,919 --> 00:27:33,486 MECHANISM. 559 00:27:33,486 --> 00:27:36,890 SO THESE TWO MECHANISMS CAN HAVE 560 00:27:36,890 --> 00:27:40,760 DIVERGENCE EFFECTS THAT CAN 561 00:27:40,760 --> 00:27:46,699 BECOME MAGNIFIED AND A MECHANISM 562 00:27:46,699 --> 00:27:48,534 TO SUPPORT HIV PERSISTENCE. 563 00:27:48,534 --> 00:27:50,103 THE CURRENT UNDERSTANDING OF THE 564 00:27:50,103 --> 00:27:51,304 MECHANISMS AND THE ROLE THEY 565 00:27:51,304 --> 00:27:53,239 PLAY IN HIV CURE STRATEGIES IS 566 00:27:53,239 --> 00:27:55,475 DISCUSSED IN MORE DETAIL IN AN 567 00:27:55,475 --> 00:28:01,114 UPCOMING REVIEW IN NATURE REVIEW 568 00:28:01,114 --> 00:28:01,414 IMMUNOLOGY. 569 00:28:01,414 --> 00:28:06,419 OUR GOAL IS TO MECHANISTICALLY 570 00:28:06,419 --> 00:28:09,722 DEFINE HOW THEY ESTABLISH 571 00:28:09,722 --> 00:28:13,726 MAINTENANCE IN CD4 T CELLS. 572 00:28:13,726 --> 00:28:15,929 WE IDENTIFIED HOW THEY REGULATE 573 00:28:15,929 --> 00:28:18,131 METABOLISM TO ENHANCE THEIR 574 00:28:18,131 --> 00:28:20,967 SURVIVAL, QUIESCENCE AND PROMOTE 575 00:28:20,967 --> 00:28:21,334 HIV LATENCY. 576 00:28:21,334 --> 00:28:24,837 SO IN THE STUDY WE ADAPTED OUR 577 00:28:24,837 --> 00:28:26,873 IN VITRO HIV LATENCY MODEL TO 578 00:28:26,873 --> 00:28:32,245 INCLUDE A CO-CULTURAL WITH CD 8 579 00:28:32,245 --> 00:28:34,314 T CELLS AND ENRICHED CELLS FROM 580 00:28:34,314 --> 00:28:36,683 HIV NAIVE INDIVIDUALS. 581 00:28:36,683 --> 00:28:38,084 WE INFECT THE CELLS IN VITRO 582 00:28:38,084 --> 00:28:40,720 WITH A REPLICATION COMPETENT HIV 583 00:28:40,720 --> 00:28:45,124 AND CO-CULTURE THEM WITH CD 8 T 584 00:28:45,124 --> 00:28:48,995 CELLS AND LOOK FOR THE IMPACT OF 585 00:28:48,995 --> 00:28:49,629 HIV INFECTION. 586 00:28:49,629 --> 00:28:52,865 ON THE TOP ROW WE'RE SHOWING 587 00:28:52,865 --> 00:28:54,567 MEMORY CD4 T CELLS IN 588 00:28:54,567 --> 00:28:56,769 MONOCULTURE AND SHOW WE SEE AN 589 00:28:56,769 --> 00:28:58,304 INCREASE IN HIV GAG EXPRESSION 590 00:28:58,304 --> 00:29:01,741 AND A DOWN MODULATION OF SURFACE 591 00:29:01,741 --> 00:29:01,908 CD4. 592 00:29:01,908 --> 00:29:05,078 IN THE BOTTOM ARE MEMORY CD4 593 00:29:05,078 --> 00:29:11,651 TVRL T CELLS WITH AUTOLOGOUS 594 00:29:11,651 --> 00:29:14,754 WITH A RATIO AND A LOSS OF HIV 595 00:29:14,754 --> 00:29:15,054 EXPRESSION. 596 00:29:15,054 --> 00:29:16,756 THE DATA SUPPORT USING THE IN 597 00:29:16,756 --> 00:29:18,024 VITRO ASSAY AS A MODEL TO LOOK 598 00:29:18,024 --> 00:29:25,798 AT THE MECHANISM OF THIS NON 599 00:29:25,798 --> 00:29:26,766 CYTOLYTIC APPROACH. 600 00:29:26,766 --> 00:29:27,967 USING AN RNA SEQ APPROACH WE 601 00:29:27,967 --> 00:29:29,869 WANTED TO LOOK AT THE CHANGES IN 602 00:29:29,869 --> 00:29:34,307 THE PROFILE OF THE CD4 T CELLS 603 00:29:34,307 --> 00:29:34,941 ASSOCIATED WITH HIV EXPRESSION. 604 00:29:34,941 --> 00:29:38,277 AND WHAT WE FOUND IS THAT 605 00:29:38,277 --> 00:29:40,646 PATHWAYS ASSOCIATED WITH 606 00:29:40,646 --> 00:29:43,016 CELLULAR METABOLISM EFFECTER 607 00:29:43,016 --> 00:29:46,452 FUNCTION AND CELL SURVIVAL ARE 608 00:29:46,452 --> 00:29:50,790 DOWN REGULATED IN CD4 T CELLS 609 00:29:50,790 --> 00:29:51,924 AND THIS IS INDICATED BY THE 610 00:29:51,924 --> 00:29:56,496 GREEN BOX. 611 00:29:56,496 --> 00:29:58,264 THESE WERE COMPARED TO CD4 T 612 00:29:58,264 --> 00:30:01,300 CELLS FROM MONOCULTURES FROM THE 613 00:30:01,300 --> 00:30:03,069 SAME INDIVIDUALS INDICATED BY 614 00:30:03,069 --> 00:30:04,270 THE ORANGE BARS. 615 00:30:04,270 --> 00:30:05,338 IT'S IMPORTANT TO NOTE THE 616 00:30:05,338 --> 00:30:09,142 SIGNALLING PATHWAYS THAT WERE 617 00:30:09,142 --> 00:30:10,510 DOWN REGULATED ARE COMING FROM 618 00:30:10,510 --> 00:30:12,445 IN THESE OBSERVATIONS ARE THE 619 00:30:12,445 --> 00:30:14,347 ONES THAT ARE ASSOCIATED OR 620 00:30:14,347 --> 00:30:15,648 CORRELATED WITH A DOWN 621 00:30:15,648 --> 00:30:18,284 REGULATION OF HIV TRANSCRIPT 622 00:30:18,284 --> 00:30:18,785 LEVELS. 623 00:30:18,785 --> 00:30:21,788 BUT WE ALSO NOTICED THERE WERE 624 00:30:21,788 --> 00:30:23,489 PATHWAYS UPREGULATED IN CD4 T 625 00:30:23,489 --> 00:30:24,590 CELLS FROM CO-CULTURES AND THESE 626 00:30:24,590 --> 00:30:28,561 WERE PATHWAYS ASSOCIATED WITH 627 00:30:28,561 --> 00:30:29,062 QUIESENCE, MEMORY AND 628 00:30:29,062 --> 00:30:30,797 DIFFERENTIATION AND IT'S THE UP 629 00:30:30,797 --> 00:30:32,698 REGULATION OF THESE PATHWAYS 630 00:30:32,698 --> 00:30:34,233 ASSOCIATED WITH A DECREASE IN 631 00:30:34,233 --> 00:30:34,934 HIV TRANSCRIPT LEVELS. 632 00:30:34,934 --> 00:30:40,306 I WANT TO POINT ONE WAS 633 00:30:40,306 --> 00:30:41,574 DISCUSSED YESTERDAY IN A 634 00:30:41,574 --> 00:30:46,212 PRESENTATION BY BRAD JONES WHERE 635 00:30:46,212 --> 00:30:49,182 HE SHOWED IT'S IMPORTANT FOR CD4 636 00:30:49,182 --> 00:30:51,184 T CELL SURVIVAL DURING HIV 637 00:30:51,184 --> 00:30:51,484 INFECTION. 638 00:30:51,484 --> 00:30:54,821 SO IN OUR ANALYSES WE IDENTIFIED 639 00:30:54,821 --> 00:30:57,390 TWO PATHWAYS CRITICAL FOR THIS 640 00:30:57,390 --> 00:31:03,596 CD 8 MEDIATED ACTIVITY. 641 00:31:03,596 --> 00:31:10,403 THAT IS BETA SIGNAL AND WINT 642 00:31:10,403 --> 00:31:18,611 STHIFT PROGRAMMING AND INDEED 643 00:31:18,611 --> 00:31:24,750 WNT SHIFT ARE KNOWN TO CAME 644 00:31:24,750 --> 00:31:30,656 PRETONE COMPLEX TO RECRUIT 645 00:31:30,656 --> 00:31:31,157 COFACTORS. 646 00:31:31,157 --> 00:31:33,392 ANOTHER INVESTIGATOR IN THE 647 00:31:33,392 --> 00:31:35,495 RECENT COLLABORATORY FOLLOWED UP 648 00:31:35,495 --> 00:31:38,498 WITH THIS DURING EPIGENETIC 649 00:31:38,498 --> 00:31:41,400 PROFILING OF THE HIV PRIME LTR 650 00:31:41,400 --> 00:31:43,736 IN CD4 T CELLS USING A 651 00:31:43,736 --> 00:31:45,304 CO-CULTURE MODEL SIMILAR TO THE 652 00:31:45,304 --> 00:31:52,245 ONE WE USED ON CD4 AND CD 8 T 653 00:31:52,245 --> 00:31:53,746 CELLS IN VITRO AND LOOKED AT 654 00:31:53,746 --> 00:31:58,317 CHIP QPCR AND LOOKED AT THE 655 00:31:58,317 --> 00:32:01,287 ACETYLATION PROFILE AND FOUND NO 656 00:32:01,287 --> 00:32:06,459 DIFFERENCE AT H3K9 AND H3K27 657 00:32:06,459 --> 00:32:08,895 WHEN LOOKING AT THE METHYLATION 658 00:32:08,895 --> 00:32:15,401 THE FOUND A DECREASE IN THE 659 00:32:15,401 --> 00:32:16,769 METHYLATION ASSOCIATED WITH 660 00:32:16,769 --> 00:32:19,372 ACTIVE PROMOTERS AND FOUND UP 661 00:32:19,372 --> 00:32:24,377 REGULATION IN H3K9 AND K27 662 00:32:24,377 --> 00:32:30,249 TRIMETHYLATION WHICH ARE MARKS 663 00:32:30,249 --> 00:32:34,053 ASSOCIATED WITH INACTIVE 664 00:32:34,053 --> 00:32:36,455 PROMOTERS AND LOOKED AT THE 665 00:32:36,455 --> 00:32:37,857 CULTURE OF HIV TRANSCRIPTION AND 666 00:32:37,857 --> 00:32:39,492 FOUND THERE WAS A SIGNIFICANT 667 00:32:39,492 --> 00:32:43,629 DECREASE IN THE RECRUITMENT OF 668 00:32:43,629 --> 00:32:44,730 TRANSCRIPTIONAL ACTIVATORS AND 669 00:32:44,730 --> 00:32:47,033 SIGNIFICANT DECREASE IN 670 00:32:47,033 --> 00:32:50,903 RECRUITMENT OF RNA POLYMERASE 2 671 00:32:50,903 --> 00:32:52,705 AND KDK9 AND INTERESTINGLY AN 672 00:32:52,705 --> 00:32:56,209 INCREASED RECRUITMENT OF THE 673 00:32:56,209 --> 00:32:58,077 REPRESSIVE FACTOR UH1 TO THE 674 00:32:58,077 --> 00:33:03,182 PROMOTER IN CD 8 T CELLS AND 675 00:33:03,182 --> 00:33:04,050 CO-CULTURE. 676 00:33:04,050 --> 00:33:05,985 AND THERE'S AN EPIGENETIC 677 00:33:05,985 --> 00:33:09,789 REGULATOR THAT HELPS MAINTAIN 678 00:33:09,789 --> 00:33:11,490 HISTOMODIFICATIONS AND DNA 679 00:33:11,490 --> 00:33:11,824 METHYLATION. 680 00:33:11,824 --> 00:33:13,159 TOGETHER WE HAVE INFORMATION 681 00:33:13,159 --> 00:33:17,163 THAT SHOWS IF YOU ARE MODULATING 682 00:33:17,163 --> 00:33:20,166 TGF BETA AND PATHWAYS THROUGH CD 683 00:33:20,166 --> 00:33:25,871 8 MECHANISMS THIS IS IMPACTING 684 00:33:25,871 --> 00:33:26,405 CHROMATIN ACCESSIBILITY 685 00:33:26,405 --> 00:33:30,209 RESULTING IN A DECREASE IN DNA 686 00:33:30,209 --> 00:33:33,346 HIV AND PROTEIN BUT IMPORTANTLY 687 00:33:33,346 --> 00:33:35,781 NOT IMPACTING THE FREQUENCY OF 688 00:33:35,781 --> 00:33:38,417 CELLS CARRYING INTEGRATED HIV 689 00:33:38,417 --> 00:33:42,355 DNA. 690 00:33:42,355 --> 00:33:46,425 TOGETHER OUR RESULTS HAVE 691 00:33:46,425 --> 00:33:49,061 UNCOVERED A POTENTIAL FOR A 692 00:33:49,061 --> 00:33:50,529 SHOCK AND KILL STRATEGY TO 693 00:33:50,529 --> 00:33:53,666 TARGET THE REPRESSION MACHINERY 694 00:33:53,666 --> 00:33:56,402 LIKE TO RELEASE VIRAL FROM THE 695 00:33:56,402 --> 00:33:58,871 PRESENCE OF CD 8 T CELLS AND 696 00:33:58,871 --> 00:34:02,842 THEN USED IN COMBINATION WITH AN 697 00:34:02,842 --> 00:34:05,177 IMMUNOLOGICAL MODULATOR TO 698 00:34:05,177 --> 00:34:10,916 AUGMENT THE CYTOTOXIC KILLING OF 699 00:34:10,916 --> 00:34:13,119 CD 8 T CELLS WE CAN IMPACT THE 700 00:34:13,119 --> 00:34:13,653 FREQUENCY. 701 00:34:13,653 --> 00:34:18,391 I WOULD LIKE TO ACKNOWLEDGE THE 702 00:34:18,391 --> 00:34:22,728 FORMER POSTDOC IN THE LAB WHO 703 00:34:22,728 --> 00:34:31,003 LED THE STUDIES. 704 00:34:31,003 --> 00:34:33,806 I THINK IT'S VERY IMPORTANT TO 705 00:34:33,806 --> 00:34:34,407 ACKNOWLEDGE THE CONTINUING 706 00:34:34,407 --> 00:34:38,411 SUPPORT OF NIH FOR STUDIES LIKE 707 00:34:38,411 --> 00:34:39,879 THESE IN PARTICULAR NIAID. 708 00:34:39,879 --> 00:34:41,547 PEOPLE LIVING WITH HIV IN THIS 709 00:34:41,547 --> 00:34:43,549 WORLD ARE COUNTING ON US TO 710 00:34:43,549 --> 00:34:46,452 CONTINUE OUR WORK NO MATTER WHO 711 00:34:46,452 --> 00:34:47,887 THE PRESIDENT IS AND WE CAN'T 712 00:34:47,887 --> 00:34:50,389 LED THEM DOWN. 713 00:34:50,389 --> 00:35:00,566 THANK YOU. 714 00:35:09,141 --> 00:35:09,675 S 715 00:35:09,675 --> 00:35:14,380 >> I'LL DESCRIBE NEW WORK WE'VE 716 00:35:14,380 --> 00:35:15,448 BEEN DOING WITH THE ERASE 717 00:35:15,448 --> 00:35:18,484 COLLABORATORY AND TALKING ABOUT 718 00:35:18,484 --> 00:35:21,620 CD 8 T CELLS AND THE GOALS OF 719 00:35:21,620 --> 00:35:26,125 OUR STUDY ARE STARTING FROM 720 00:35:26,125 --> 00:35:33,666 THECYTEEE -- CYTOTOXIC TISSUES 721 00:35:33,666 --> 00:35:37,470 AND TARGET CYTOTOXIC CD 8 T 722 00:35:37,470 --> 00:35:40,639 CELLS TO ULTIMATELY ELIMINATE 723 00:35:40,639 --> 00:35:41,107 HIV INFECTED CELLS. 724 00:35:41,107 --> 00:35:45,311 SO WHAT WE LEARNED IS THAT WE 725 00:35:45,311 --> 00:35:48,848 CAN TARGET DIRECTLY CYTOTOXIC CD 726 00:35:48,848 --> 00:35:51,417 8 T CELLS IN HUMANS, MICE AND 727 00:35:51,417 --> 00:35:56,522 NONHUMAN PRIMATES AND TARGET 728 00:35:56,522 --> 00:35:58,224 PROTEINS USING THE mRNA 729 00:35:58,224 --> 00:36:00,960 TECHNOLOGY TO ENABLE THE IMMUNE 730 00:36:00,960 --> 00:36:03,796 SYSTEM TO CONTROL OR AFFECT HIV 731 00:36:03,796 --> 00:36:05,698 INFECTED CELLS IN TISSUES. 732 00:36:05,698 --> 00:36:09,068 THE BACKGROUND IS THAT FULLY 733 00:36:09,068 --> 00:36:10,970 DIFFERENTIATING THE CELLS DO NOT 734 00:36:10,970 --> 00:36:13,172 MIGRATE TO TISSUES TO ELIMINATE 735 00:36:13,172 --> 00:36:14,874 HIV RESERVOIRS AND THIS HAS BEEN 736 00:36:14,874 --> 00:36:17,209 KNOWN FOR A LONG TIME THEY 737 00:36:17,209 --> 00:36:19,245 DIFFERENTIATE TO CYTOTOXIC 738 00:36:19,245 --> 00:36:19,512 EFFECTERS. 739 00:36:19,512 --> 00:36:23,416 THEY LOSE THE EXPRESSION OF THE 740 00:36:23,416 --> 00:36:26,652 HOMING MOLECULES BEING CD 62L 741 00:36:26,652 --> 00:36:28,254 AND 7 THAT ALLOW THEM TO BE 742 00:36:28,254 --> 00:36:32,158 ATTRACTED TO AND ENTER THE LYMPH 743 00:36:32,158 --> 00:36:36,028 NODE AND SOME WAS WORK DONE BY 744 00:36:36,028 --> 00:36:36,662 LUIS BACK THERE. 745 00:36:36,662 --> 00:36:41,167 THE STUDY GOAL WAS TO FIGURE OUT 746 00:36:41,167 --> 00:36:43,269 A WAY TO RE-EXPRESS ON 747 00:36:43,269 --> 00:36:47,206 PERIPHERAL BLOOD TO ALLOW THEM 748 00:36:47,206 --> 00:36:48,841 TO TRAFFIC IN LYMPHOID TISSUES 749 00:36:48,841 --> 00:36:51,710 AND WE WANTED THIS TO WORK 750 00:36:51,710 --> 00:36:52,511 ULTIMATELY BE SOMETHING THAT 751 00:36:52,511 --> 00:36:55,614 COULD BE TRANSLATED INTO HUME 752 00:36:55,614 --> 00:36:58,517 ZWRANZ AND SO OUR FIRST STEP 753 00:36:58,517 --> 00:37:02,188 WHICH WAS BASICALLY TO DEVELOP A 754 00:37:02,188 --> 00:37:05,758 PLATFORM TO TARGET HUMAN CTL TO 755 00:37:05,758 --> 00:37:11,564 EXPRESS EXOGENOUS PROTEINS IN 756 00:37:11,564 --> 00:37:13,299 VIVO AND WE HAVE TO WORK OUR WAY 757 00:37:13,299 --> 00:37:14,700 TOWARDS THAT. 758 00:37:14,700 --> 00:37:19,939 OUR STRATEGY WAS TO USE TARGETED 759 00:37:19,939 --> 00:37:21,640 mRNA PARTICLES TO DELIVER TO 760 00:37:21,640 --> 00:37:21,807 CTL. 761 00:37:21,807 --> 00:37:23,442 THE FIRST CHALLENGE WAS HOW TO 762 00:37:23,442 --> 00:37:25,211 TARGET THE CELLS. 763 00:37:25,211 --> 00:37:30,916 AND WE SETTLED ON A REPRESENTER 764 00:37:30,916 --> 00:37:35,221 CALLED CX3CR1 AND THIS IS A 765 00:37:35,221 --> 00:37:37,356 RECEPTOR THAT IS ACTUALLY 766 00:37:37,356 --> 00:37:47,867 EXPRESSED HIGHLY BY VASCULAR 767 00:37:51,170 --> 00:37:53,506 CYTOTOXIC EFFECT AND HAS SOME 768 00:37:53,506 --> 00:38:01,780 EXPRESSION OUTSIDE THE 769 00:38:01,780 --> 00:38:02,982 HEMATOPOIETIC SYSTEM. 770 00:38:02,982 --> 00:38:03,916 AND THERE'S A MEMBRANE THAT 771 00:38:03,916 --> 00:38:10,322 STAYS ON THE INSIDE THE BLOOD 772 00:38:10,322 --> 00:38:12,124 VESSEL OR COULD BE CLEAVED. 773 00:38:12,124 --> 00:38:14,026 HOW WOULD WE THEN USE THE 774 00:38:14,026 --> 00:38:14,260 ACCESS? 775 00:38:14,260 --> 00:38:15,528 SO THERE'S A NUMBER OF DIFFERENT 776 00:38:15,528 --> 00:38:18,297 WAYS YOU CAN TARGET LNP TO CELL 777 00:38:18,297 --> 00:38:18,497 TYPES. 778 00:38:18,497 --> 00:38:20,466 WE HEARD ABOUT SOME OF THEM IN 779 00:38:20,466 --> 00:38:23,002 THE TALKS SO FAR THIS WEEK 780 00:38:23,002 --> 00:38:25,170 INCLUDING MODIFYING THE LIPIDS 781 00:38:25,170 --> 00:38:26,906 OR USING ANTIBODIES TO BIND TO 782 00:38:26,906 --> 00:38:27,740 THE LNPs. 783 00:38:27,740 --> 00:38:30,643 WE DECIDED TO TAKE A DIFFERENT 784 00:38:30,643 --> 00:38:33,812 STRATEGY AND DIRECTLY CONJUGATE 785 00:38:33,812 --> 00:38:38,817 THE LIGAND ON TO THE LNP IN A 786 00:38:38,817 --> 00:38:43,556 DIRECT CONJUGATION THEM METHOD 787 00:38:43,556 --> 00:38:45,357 AND AS OUR FIRST EXPERIMENT 788 00:38:45,357 --> 00:38:46,358 BECAUSE IF THIS DIDN'T WORK 789 00:38:46,358 --> 00:38:53,098 THERE WAS NO POINT IN GOING 790 00:38:53,098 --> 00:38:53,799 FORWARD AND THEY ARE WERE 791 00:38:53,799 --> 00:38:57,202 EXPRESSION THE REPORTER AND WE 792 00:38:57,202 --> 00:39:00,606 INCUBATED THEM WITH PRIMARY 793 00:39:00,606 --> 00:39:02,908 HUMAN PERIPHERAL BLOOD 794 00:39:02,908 --> 00:39:05,578 LYMPHOCYTES AND THE FIRST 795 00:39:05,578 --> 00:39:06,645 EXPERIMENT WAS A HOME RUN MORE 796 00:39:06,645 --> 00:39:09,181 THAN EXPECTED. 797 00:39:09,181 --> 00:39:11,850 ON THE LEFT PLOT WE'RE SEWING 798 00:39:11,850 --> 00:39:13,419 PRIMARY HUMAN CD 8 T CELLS AND 799 00:39:13,419 --> 00:39:17,222 SHOWING THE RECEPTOR WE WANT TO 800 00:39:17,222 --> 00:39:20,159 TARGET ON THE Y AXIS AND ADD THE 801 00:39:20,159 --> 00:39:23,062 LNPs AND INCUBATE THE CELLS FOR 802 00:39:23,062 --> 00:39:24,330 ABOUT THREE DAYS. 803 00:39:24,330 --> 00:39:25,564 WE CAN SEE ESSENTIALLY A MASSIVE 804 00:39:25,564 --> 00:39:30,269 LOSS OF THE RECEPTOR AS IT'S 805 00:39:30,269 --> 00:39:34,840 INDUCED TO ENDOCYTOSIS AND SEE 806 00:39:34,840 --> 00:39:37,643 AN EXPRESSION OF GFP BY THE 807 00:39:37,643 --> 00:39:41,213 CELLS WITHOUT ADDING 808 00:39:41,213 --> 00:39:41,814 STIMULATION, CYTOKINE JUST 809 00:39:41,814 --> 00:39:43,882 ADDING TO THE CD 8s AND PUTTING 810 00:39:43,882 --> 00:39:45,250 THEM IN CULTURE. 811 00:39:45,250 --> 00:39:46,585 JUST TO PROVE THIS IS TARGETING 812 00:39:46,585 --> 00:39:50,289 THE CELLS WE WANTED, WE THEN 813 00:39:50,289 --> 00:39:51,991 SUBSET MEMORY PHENOTYPES OF THE 814 00:39:51,991 --> 00:39:55,594 CELLS AND CAN SHOW CLEARLY GFP 815 00:39:55,594 --> 00:39:57,963 ON THE RIGHT FLOW PLOTS IS 816 00:39:57,963 --> 00:40:00,899 GETTING EXCLUSIVELY EXPRESSED IN 817 00:40:00,899 --> 00:40:05,704 THE EFFECTER MEMORY, NOT 100% OF 818 00:40:05,704 --> 00:40:10,576 THEM BUT IMPORTANTLY THOSE CELLS 819 00:40:10,576 --> 00:40:14,446 THAT EXPRESSED THE T CELLS THAT 820 00:40:14,446 --> 00:40:17,483 EXPRESSED ON THE BOTTOM LEFT 821 00:40:17,483 --> 00:40:20,519 WITHOUT AN LNP ADDED WE HAVE 822 00:40:20,519 --> 00:40:22,187 EXPRESSION FROM THE CELLS 37 823 00:40:22,187 --> 00:40:28,027 WHEN WE RAD THE LNP AND SEE XFP 824 00:40:28,027 --> 00:40:30,396 EXPRESSION CELLS WE SEE 825 00:40:30,396 --> 00:40:32,831 INDICATION WE'RE TARGETING 826 00:40:32,831 --> 00:40:34,867 CYTOTOXIC CELLS AND NOT INDUCING 827 00:40:34,867 --> 00:40:35,601 DEGRANULATION OF THE CELLS. 828 00:40:35,601 --> 00:40:37,102 WE THEN WANTED TO TAKE IT IN 829 00:40:37,102 --> 00:40:37,302 VIVO. 830 00:40:37,302 --> 00:40:41,573 WE PUT IT INTO MICE AND LCMV 831 00:40:41,573 --> 00:40:43,075 MODEL AND I DON'T HAVE TIME TO 832 00:40:43,075 --> 00:40:45,010 TALK TOO MUCH ABOUT THE MODEL 833 00:40:45,010 --> 00:40:47,146 PUT BASICALLY YOU CAN SEE EIGHT 834 00:40:47,146 --> 00:40:51,650 DAYS AFTER LCM INFECTION WE ADD 835 00:40:51,650 --> 00:40:55,120 LMP AND 24 HOURS LATER WE SEE A 836 00:40:55,120 --> 00:40:58,090 MASSIVE UPTAKE INTO THE RECEPTOR 837 00:40:58,090 --> 00:41:00,859 POSITIVE CELLS WITH AN 80% 838 00:41:00,859 --> 00:41:01,627 TARGETING IN VIVO AFTER ONE DOSE 839 00:41:01,627 --> 00:41:04,063 IN THE MICE. 840 00:41:04,063 --> 00:41:09,034 WE THEN TOOK THIS WITH THE 841 00:41:09,034 --> 00:41:10,235 MONKEYS BECAUSE WE'RE TRYING TO 842 00:41:10,235 --> 00:41:12,304 GO FAST AND SO THIS IS A 843 00:41:12,304 --> 00:41:13,138 TWO-ANIMAL EXPERIMENT. 844 00:41:13,138 --> 00:41:15,674 I'M SHOWING FLOW DATA FROM ONE 845 00:41:15,674 --> 00:41:17,042 REPRESENTATIVE ANIMAL AND NOW 846 00:41:17,042 --> 00:41:21,914 WE'RE IN A REALISTIC SITUATION. 847 00:41:21,914 --> 00:41:22,715 THE ANIMALS DON'T HAVE 848 00:41:22,715 --> 00:41:26,018 EXPRESSION AND 15% OF THE 849 00:41:26,018 --> 00:41:28,253 CIRCULATING CD 8s HAVE RECEPTOR 850 00:41:28,253 --> 00:41:30,656 AFTER A SINGLE DAY WITH ONE DOSE 851 00:41:30,656 --> 00:41:31,423 DELIVERED I.D. WE HAVE COMPLETE 852 00:41:31,423 --> 00:41:33,892 LOSS OF THE RECEPTOR AND 853 00:41:33,892 --> 00:41:35,360 EQUIVALENT LEVEL OF CELLS 854 00:41:35,360 --> 00:41:38,964 PRODUCING GFP AND THIS PERSISTED 855 00:41:38,964 --> 00:41:40,499 UNTIL DAY 7. 856 00:41:40,499 --> 00:41:42,401 I'M NOT SHOWING DAY 10 AND EVEN 857 00:41:42,401 --> 00:41:45,938 DAY 14 WE SEE RESIDUAL 858 00:41:45,938 --> 00:41:48,307 EXPRESSION AND TARGETS 100% OF 859 00:41:48,307 --> 00:41:50,242 THE SUBSET OF CELLS TARGETED IN 860 00:41:50,242 --> 00:41:52,745 VIVO AND PERSISTS FOR HALF LIFE 861 00:41:52,745 --> 00:41:55,481 OF GFP AS A CRITICAL ISSUE. 862 00:41:55,481 --> 00:41:57,249 THE PERSISTS FOR A LONG TIME. 863 00:41:57,249 --> 00:41:58,917 AND WE CAN SHOW THIS IS VERY 864 00:41:58,917 --> 00:42:02,387 SPECIFICALLY TARGETING THE 865 00:42:02,387 --> 00:42:03,555 EFFECTER CELLS IN THE MONKEYS AS 866 00:42:03,555 --> 00:42:07,526 WELL AND I HAVEN'T TALKED ABOUT 867 00:42:07,526 --> 00:42:14,233 NK CELLS BUT 100% OF THE 868 00:42:14,233 --> 00:42:20,139 REFLECTOR CELLS AS WELL. 869 00:42:20,139 --> 00:42:22,407 THIS IS AN IN VITRO. 870 00:42:22,407 --> 00:42:29,214 WE'RE USING A CONSTRUCT mRNA 871 00:42:29,214 --> 00:42:31,150 WITH A STEADY AND DEFICIENT 872 00:42:31,150 --> 00:42:34,253 MUTANT SO THEY DON'T LOSE IT AND 873 00:42:34,253 --> 00:42:38,490 THIS IS SHOWING HUMAN EXPRESSION 874 00:42:38,490 --> 00:42:41,026 ON PRIMARY MACAQUE CELLS IN 875 00:42:41,026 --> 00:42:41,794 VITRO. 876 00:42:41,794 --> 00:42:52,304 YOU CAN SEE THEY'RE TRITATING 877 00:42:54,873 --> 00:43:01,580 AND WE GET TRAFFICKING IN IN 878 00:43:01,580 --> 00:43:12,124 VIVO IN A COUPLE WEEKS TEACHING 879 00:43:21,233 --> 00:43:22,367 US THE PROTOCOLS AND DRIVING THE 880 00:43:22,367 --> 00:43:32,511 STUDIES. 881 00:43:34,112 --> 00:43:36,014 >> I'M JUST GOING TO CONCLUDE 882 00:43:36,014 --> 00:43:38,917 WITH A COUPLE SLIDES AND YOU SAW 883 00:43:38,917 --> 00:43:40,686 IN OUR TALKS WE IDENTIFIED 884 00:43:40,686 --> 00:43:45,457 MULTIPLE MECHANISMS THAT PRO 885 00:43:45,457 --> 00:43:47,226 PROMOTED THE LONG-TERM SURVIVAL 886 00:43:47,226 --> 00:43:49,294 AND TRANSLATING THE DISCOVERY 887 00:43:49,294 --> 00:43:54,700 FROM THE INSIGHT TO 888 00:43:54,700 --> 00:44:04,943 INTERVENTION. 889 00:44:07,012 --> 00:44:07,946 WE'RE MOVING TO THE NONHUMAN 890 00:44:07,946 --> 00:44:09,848 PRIMATES AND THE INTERVENTION 891 00:44:09,848 --> 00:44:11,884 WE'RE DOING PERFORMING DIFFERENT 892 00:44:11,884 --> 00:44:14,386 PHASE OF THE COURSE OF THE 893 00:44:14,386 --> 00:44:19,191 INFECTION IN THE ANIMALS AND THE 894 00:44:19,191 --> 00:44:21,760 MECHANISTIC FACTION OF 895 00:44:21,760 --> 00:44:23,228 INTERVENTION AND IDENTIFIED 896 00:44:23,228 --> 00:44:26,632 INTERVENTION AT THE INITIATION 897 00:44:26,632 --> 00:44:28,700 FOR EXAMPLE THE RATIONALE IS TO 898 00:44:28,700 --> 00:44:33,538 ELIMINATE THE INFECTED CELLS 899 00:44:33,538 --> 00:44:35,207 THAT OTHERWISE WOULD BE THE 900 00:44:35,207 --> 00:44:36,775 RESERVOIR AND TESTING AND 901 00:44:36,775 --> 00:44:37,542 CHARACTERIZING THE INTERVENTION 902 00:44:37,542 --> 00:44:46,418 AND THIS IS WITH A STUDY TO 903 00:44:46,418 --> 00:44:49,254 INDUCE REACTIVATION AND THE 904 00:44:49,254 --> 00:44:51,823 RESERVOIR AND DOING INTERVENTION 905 00:44:51,823 --> 00:44:54,793 OF THE BLOCKADE TARGETED 906 00:44:54,793 --> 00:44:58,397 INTERACTION INTO NOW IMPROVING 907 00:44:58,397 --> 00:45:04,937 THE ABILITY TO REBOUND THE 908 00:45:04,937 --> 00:45:05,137 VIRUS. 909 00:45:05,137 --> 00:45:13,278 REALLY WE HAVE INTERVENTION AND 910 00:45:13,278 --> 00:45:19,885 BLOCKADE OF IL10 THAT IMPROVED 911 00:45:19,885 --> 00:45:22,087 THE REBOUND. 912 00:45:22,087 --> 00:45:28,327 AND THE HOPE WITH WE BE ABLE TO 913 00:45:28,327 --> 00:45:30,562 LOWER THE RESERVOIR WITH THE 914 00:45:30,562 --> 00:45:31,496 INITIATION IN THE FULLY 915 00:45:31,496 --> 00:45:33,365 EXPRESSED ANIMAL AND LOWER THE 916 00:45:33,365 --> 00:45:34,599 RESERVOIR AND INCLUDING THE 917 00:45:34,599 --> 00:45:38,036 ABILITY OF THE ADMINISTRATION TO 918 00:45:38,036 --> 00:45:39,972 CONTROL THE VIRUS AND HAVING THE 919 00:45:39,972 --> 00:45:41,340 REMISSION OF HIV. 920 00:45:41,340 --> 00:45:43,375 WHEN WE TALK ABOUT COMBINED 921 00:45:43,375 --> 00:45:44,343 INTERVENTION IT'S IMPORTANT TO 922 00:45:44,343 --> 00:45:47,212 REMEMBER THE NON-SPECIFIC 923 00:45:47,212 --> 00:45:51,917 DELIVERY MAY CONTRIBUTE TO 924 00:45:51,917 --> 00:45:57,556 TOXICITY OR ANTAGONISTIC EFFECT. 925 00:45:57,556 --> 00:46:02,394 WE HAVE IDENTIFIED IS IT GOOD TO 926 00:46:02,394 --> 00:46:10,836 HAVE STEM CELLS BUT CD4 CELLS 927 00:46:10,836 --> 00:46:13,305 AND MANY THERE'S A SUBSET AND 928 00:46:13,305 --> 00:46:15,073 THESE ARE THE IMMUNOCELLS. 929 00:46:15,073 --> 00:46:18,410 IT'S IMPORTANT TO MOVE THROUGH 930 00:46:18,410 --> 00:46:20,679 SELECTIVE DRUG DELIVERY TO 931 00:46:20,679 --> 00:46:22,347 SPECIFIC DRUG SUBSET AND THIS IS 932 00:46:22,347 --> 00:46:25,484 THE WORK WE'RE PLANNING TO DO IN 933 00:46:25,484 --> 00:46:27,652 THE CONTINUATION IN THE NEXT FEW 934 00:46:27,652 --> 00:46:29,154 YEARS AND THIS IS THE STRATEGY 935 00:46:29,154 --> 00:46:29,921 WE'RE GOING TO MOVE IN THE 936 00:46:29,921 --> 00:46:35,394 FUTURE AND ONE OF THE METHODS IS 937 00:46:35,394 --> 00:46:42,167 USING mRNA CELL SPECIFIC 938 00:46:42,167 --> 00:46:43,635 DELIVERY AND CELLS HAVE A 939 00:46:43,635 --> 00:46:44,536 COMBINED STRATEGY IN NONHUMAN 940 00:46:44,536 --> 00:46:47,606 PRIMATE AND CHARACTERIZED THE 941 00:46:47,606 --> 00:46:50,208 INTERVENTION AND COMBINE THE 942 00:46:50,208 --> 00:46:53,145 EFFICACY PROFILE AND TRANSLATE 943 00:46:53,145 --> 00:46:55,714 THE MOST SAFE AND EFFECTIVE 944 00:46:55,714 --> 00:46:56,048 STRATEGY. 945 00:46:56,048 --> 00:46:58,717 SO WITH THAT I WOULD LIKE TO 946 00:46:58,717 --> 00:47:00,852 ACKNOWLEDGE ALL THE MEMBER OF 947 00:47:00,852 --> 00:47:02,888 THE COLLABORATORY THAT 948 00:47:02,888 --> 00:47:05,457 PARTICIPATE IN THESE AND OTHER 949 00:47:05,457 --> 00:47:08,727 STUDY. 950 00:47:08,727 --> 00:47:17,235 I WANT TO THANK THE MEMBERS AND 951 00:47:17,235 --> 00:47:20,906 SAB MEMBERS AND OF COURSE AND 952 00:47:20,906 --> 00:47:24,109 ALL THE INSTITUTION AT NIH FOR 953 00:47:24,109 --> 00:47:24,342 SUPPORT. 954 00:47:24,342 --> 00:47:34,686 THANK YOU VERY MUCH. 955 00:48:08,353 --> 00:48:10,755 >> WE DID AN EXPERIMENT WITH THE 956 00:48:10,755 --> 00:48:13,492 CD 8 T CELLS AND PUT THE 957 00:48:13,492 --> 00:48:17,095 CULTURES PACK IN TO LOOK AT 958 00:48:17,095 --> 00:48:19,297 WHETHER WE CAN REACTIVATE THE 959 00:48:19,297 --> 00:48:21,700 VIRUS AND 42 CD4s THAT WENT BACK 960 00:48:21,700 --> 00:48:24,569 INTO CULTURE STAYED WITH THE LOW 961 00:48:24,569 --> 00:48:26,004 LEVEL OR HIV EXPRESSION BUT IF 962 00:48:26,004 --> 00:48:30,408 WE ACTIVATED THEM WE COULD 963 00:48:30,408 --> 00:48:31,576 REACTIVATE THEM AS LONG AS THE 964 00:48:31,576 --> 00:48:33,011 CD 8s WERE REMOVED. 965 00:48:33,011 --> 00:48:34,412 THERE WAS AN EXPERIMENT TO SEE 966 00:48:34,412 --> 00:48:36,214 COULD WE DO IT BUT THAT'S 967 00:48:36,214 --> 00:48:39,651 SOMETHING WE NEED TO FOLLOW UP 968 00:48:39,651 --> 00:48:42,220 WITH CAREEN SEE THE STABILITY OF 969 00:48:42,220 --> 00:48:44,823 THE EPIGENETIC MARKS. 970 00:48:44,823 --> 00:48:47,859 >> THANK YOU, SHARON LEWIN AND 971 00:48:47,859 --> 00:48:49,861 ALL GREAT TALKS AND FABULOUS 972 00:48:49,861 --> 00:48:50,061 WORK. 973 00:48:50,061 --> 00:48:54,299 MY QUESTION IS FOR GUIDO. 974 00:48:54,299 --> 00:48:56,501 WONDERFUL TO SEE THE MEDICATION 975 00:48:56,501 --> 00:48:59,137 WORKING AT ART INITIATION. 976 00:48:59,137 --> 00:49:02,407 THE DIFFERENCE BETWEEN THE VIRAL 977 00:49:02,407 --> 00:49:05,043 LOAD CLEARANCE AND THE RESERVOIR 978 00:49:05,043 --> 00:49:07,746 FINDINGS ARE VERY INTRIGUING AND 979 00:49:07,746 --> 00:49:09,848 IT SHOULD SHORTEN THE SURVIVAL 980 00:49:09,848 --> 00:49:12,984 OF AN INFECTED CELL AND EXPECTED 981 00:49:12,984 --> 00:49:14,486 VIRAL LOAD CLEARANCE TO BE 982 00:49:14,486 --> 00:49:14,719 GREATER. 983 00:49:14,719 --> 00:49:16,588 IF YOU CAN ELABORATE ON THE 984 00:49:16,588 --> 00:49:17,956 THINKING THERE. 985 00:49:17,956 --> 00:49:22,594 THE SECOND QUESTION WAS THERE A 986 00:49:22,594 --> 00:49:24,896 DIFFERENCE WITH IT ALONE FOR 987 00:49:24,896 --> 00:49:27,098 WITH OUR LRA INTERVENTION. 988 00:49:27,098 --> 00:49:29,134 HOW DO YOU DESIGN THE STUDIES 989 00:49:29,134 --> 00:49:30,769 WAS HARD TO TELL. 990 00:49:30,769 --> 00:49:34,339 DID THE LRA ADD ANYTHING TO IT 991 00:49:34,339 --> 00:49:41,079 IN YOUR SECOND STUDIES? 992 00:49:41,079 --> 00:49:42,814 >> THE SECOND STUDY I FORGOT TO 993 00:49:42,814 --> 00:49:46,418 MENTION IS ALSO SUPPORTED BY AN 994 00:49:46,418 --> 00:49:48,887 RO1 GRANT I RECEIVED TO CONTINUE 995 00:49:48,887 --> 00:49:53,425 TO EXPLORE THE EFFECT OF CD 8 996 00:49:53,425 --> 00:50:03,902 DEPLETION ON VIRUS REACT -- 997 00:50:09,407 --> 00:50:09,674 REACTIVATION. 998 00:50:09,674 --> 00:50:20,218 DID -- IDEALLY WE SHOULD HAVE 12 999 00:50:24,556 --> 00:50:26,925 GROUPS IN EVERY SINGLE POSSIBLE 1000 00:50:26,925 --> 00:50:27,225 COMBINATION. 1001 00:50:27,225 --> 00:50:30,395 WE COALESCED AROUND THE IDEA OF 1002 00:50:30,395 --> 00:50:34,633 KITCHEN SINK APPROACH THAT WHEN 1003 00:50:34,633 --> 00:50:37,102 WE ADD EVERYTHING WHAT REALLY 1004 00:50:37,102 --> 00:50:37,335 HAPPENS. 1005 00:50:37,335 --> 00:50:39,037 INTERESTINGLY ENOUGH WE NEED TO 1006 00:50:39,037 --> 00:50:40,839 DO MORE ANALYSIS BUT 1007 00:50:40,839 --> 00:50:42,040 INTERESTINGLY ENOUGH IT SEEMS 1008 00:50:42,040 --> 00:50:44,109 LIKE IT'S THE DIFFERENTIATOR AT 1009 00:50:44,109 --> 00:50:46,678 THE POINT PROBABLY BECAUSE THE 1010 00:50:46,678 --> 00:50:49,281 REVERSAL INDUCED AND KNEW FROM 1011 00:50:49,281 --> 00:50:56,354 THE NATURE PAPER REVERSAL OF 1012 00:50:56,354 --> 00:50:58,923 DEPLETION DOESN'T GO TO THE 1013 00:50:58,923 --> 00:51:00,959 HARDCORE RESERVOIR. 1014 00:51:00,959 --> 00:51:08,199 BUT BENITICLAX SEEMS TO DO MORE. 1015 00:51:08,199 --> 00:51:10,402 YOU'RE SPOT ON. 1016 00:51:10,402 --> 00:51:13,938 YOU PROBABLY SHOULD JOIN US AT 1017 00:51:13,938 --> 00:51:19,511 EMORY BECAUSE WE'VE BEEN TALKING 1018 00:51:19,511 --> 00:51:24,382 IN THE PAST THREE WEEKS THE 1019 00:51:24,382 --> 00:51:27,152 PREDICTION IS THE CELLS DIE 1020 00:51:27,152 --> 00:51:37,295 FASTER. 1021 00:52:03,021 --> 00:52:09,361 AND THE AFFECT OF VENETOCLAX IS 1022 00:52:09,361 --> 00:52:19,371 PUSHING IT TO HALF LIFE. 1023 00:52:19,371 --> 00:52:22,674 WE CAN TALK MORE BUT YOU'RE SPOT 1024 00:52:22,674 --> 00:52:22,841 ON. 1025 00:52:22,841 --> 00:52:24,309 THE SIMPLISTIC EXPECT WILL 1026 00:52:24,309 --> 00:52:27,112 RESULT WOULD HAVE BEEN A FASTER 1027 00:52:27,112 --> 00:52:28,113 DECLINE OF VIREMIA. 1028 00:52:28,113 --> 00:52:32,016 WE NEED TO PROBABLY RUN SOME 1029 00:52:32,016 --> 00:52:37,722 MOUSE MODELS WITH DIFFERENT 1030 00:52:37,722 --> 00:52:38,022 ASSUMPTIONS. 1031 00:52:38,022 --> 00:52:48,566 >> I'M CURIOUS DID YOU MIX CD4 1032 00:52:48,800 --> 00:52:52,036 AND 8 TOGETHER? 1033 00:52:52,036 --> 00:52:54,272 IF YOU MIX THE CELL WITH YOUR 1034 00:52:54,272 --> 00:52:56,641 CD4 DO YOU SEE THE SAME EFFECT? 1035 00:52:56,641 --> 00:52:59,210 >> SO THAT'S A GOOD QUESTION. 1036 00:52:59,210 --> 00:53:02,414 WE HAVEN'T DONE THAT EXPERIMENT 1037 00:53:02,414 --> 00:53:06,584 BUT I WILL SAY THAT IN CARRINE'S 1038 00:53:06,584 --> 00:53:08,586 MODEL SHE USES A SIMILAR CULTURE 1039 00:53:08,586 --> 00:53:10,388 SYSTEM BUT IT'S A SLIGHTLY 1040 00:53:10,388 --> 00:53:15,427 DIFFERENT ACTIVATION MECHANISM 1041 00:53:15,427 --> 00:53:19,097 SO WHERE THEY'RE NOT SEEING THE 1042 00:53:19,097 --> 00:53:21,166 EXPANSION OF THE CD 8 T CELLS AT 1043 00:53:21,166 --> 00:53:23,701 THE CO-CULTURE IT'S A BALANCED 1044 00:53:23,701 --> 00:53:26,037 DISTRIBUTION OF THE CELLS AND 1045 00:53:26,037 --> 00:53:29,574 THEY'RE STILL SEEING THIS IMPACT 1046 00:53:29,574 --> 00:53:30,375 ON EPIGENETICS. 1047 00:53:30,375 --> 00:53:32,076 IT'S A GREAT QUESTION BECAUSE 1048 00:53:32,076 --> 00:53:34,579 IT'S SOMETHING WE THOUGHT A LOT 1049 00:53:34,579 --> 00:53:37,048 ABOUT LIKE THE CD 8'S ARE 1050 00:53:37,048 --> 00:53:38,183 ACTIVATED AND WILL 1051 00:53:38,183 --> 00:53:45,690 PROLIFERATE -- WHAT'S THAT? 1052 00:53:45,690 --> 00:53:46,424 EXACTLY. 1053 00:53:46,424 --> 00:53:50,128 WE REPEATEDLY CHANGED MEDIA AND 1054 00:53:50,128 --> 00:53:51,863 REFRESHED EVERY DAY TO MAKE SURE 1055 00:53:51,863 --> 00:53:53,531 THERE'S LOTS OF NUTRIENTS SO 1056 00:53:53,531 --> 00:53:58,870 WE'RE NOT STARVING ANYBODY. 1057 00:53:58,870 --> 00:54:02,006 AND WE TRIED TO FIGURE OUT THAT 1058 00:54:02,006 --> 00:54:02,974 MECHANISM AND BECAUSE WE HAVE 1059 00:54:02,974 --> 00:54:05,977 THE ABILITY TO LOOK AT THE 1060 00:54:05,977 --> 00:54:07,378 NONHUMAN PRIMATE AND SEE THESE 1061 00:54:07,378 --> 00:54:12,851 ARE IN PARALLEL AND WE'RE NOT 1062 00:54:12,851 --> 00:54:14,285 SEEING AN IN VITRO RESULT THAT 1063 00:54:14,285 --> 00:54:16,454 JUST CAN'T BE RECAPITULATED IN 1064 00:54:16,454 --> 00:54:19,290 VIVO AND WE STARTED WITH AN IN 1065 00:54:19,290 --> 00:54:20,625 VIVO OBSERVATION AND LOOKED TO 1066 00:54:20,625 --> 00:54:26,064 SEE HOW TO MODEL IT IN VITRO. 1067 00:54:26,064 --> 00:54:34,405 >> THERE'S LOTS OF MECHANISMS. 1068 00:54:34,405 --> 00:54:36,841 HOW DOES THAT AFFECT THE 1069 00:54:36,841 --> 00:54:37,642 MECHANISMS WE'RE SEEING TO IN 1070 00:54:37,642 --> 00:54:40,578 VIVO FINDING SHOWING THE 1071 00:54:40,578 --> 00:54:42,914 INTERACTION AND REACTIVATION IS 1072 00:54:42,914 --> 00:54:44,182 KILLING THE HIV? 1073 00:54:44,182 --> 00:54:45,783 >> SO, I GUESS -- 1074 00:54:45,783 --> 00:54:48,786 >> YOU NEED TO READ THE PAPERS. 1075 00:54:48,786 --> 00:54:53,191 WE HAVE PAPERS IN NATURE AND 1076 00:54:53,191 --> 00:54:54,459 IMMUNITY AND TWO BUT THE EASY 1077 00:54:54,459 --> 00:54:55,994 ANSWER IS YOU NEED TO PULL OUT 1078 00:54:55,994 --> 00:54:56,327 THE PAPERS. 1079 00:54:56,327 --> 00:54:58,329 I CAN SEND THEM TO YOU AND READ 1080 00:54:58,329 --> 00:54:59,864 THEM BECAUSE WE DISCUSS ALL THE 1081 00:54:59,864 --> 00:55:01,699 INTERACTION FOR THIS TYPE OF 1082 00:55:01,699 --> 00:55:02,400 INTERPRETATION. 1083 00:55:02,400 --> 00:55:11,442 IT'S A LONG STORY IT'S ABOUT 12 1084 00:55:11,442 --> 00:55:14,412 PAPERS BUT I DON'T KNOW IT'S A 1085 00:55:14,412 --> 00:55:15,780 GOOD USE OF TIME HERE TO 1086 00:55:15,780 --> 00:55:16,614 SUMMARIZE IT. 1087 00:55:16,614 --> 00:55:18,449 >> THANK YOU FOR TAKING US BACK 1088 00:55:18,449 --> 00:55:20,718 TO THE '90s BEFORE YOU WERE BORN 1089 00:55:20,718 --> 00:55:24,088 AND THE JAY LEEVY FACTOR. 1090 00:55:24,088 --> 00:55:26,391 HOW -- IT WAS GREAT YOU 1091 00:55:26,391 --> 00:55:28,927 EXPLAINED WHAT HAPPENED IN THE 1092 00:55:28,927 --> 00:55:31,296 CD4 CELLS AND LIKELY IT WOULD BE 1093 00:55:31,296 --> 00:55:33,598 ALSO GREAT IF YOU COULD TELL US 1094 00:55:33,598 --> 00:55:35,600 HOW THE CD 8 CELLS ARE DOING 1095 00:55:35,600 --> 00:55:38,836 THIS BECAUSE IT WOULD BE GREAT 1096 00:55:38,836 --> 00:55:41,472 TO BLOCK THAT TEMPORARILY 1097 00:55:41,472 --> 00:55:43,341 OPPOSED TO KILLING CD 8 T CELLS 1098 00:55:43,341 --> 00:55:44,008 WITH THE ANTIBODY. 1099 00:55:44,008 --> 00:55:46,611 DID YOU FIND THE FACTOR OR WHAT 1100 00:55:46,611 --> 00:55:51,916 IS IT THAT CD 8s ARE DOING THAT 1101 00:55:51,916 --> 00:55:55,153 CHANGES THE BIOLOGY OF THESE CD4 1102 00:55:55,153 --> 00:55:55,420 CELLS. 1103 00:55:55,420 --> 00:55:57,922 >> SO IT'S THE TGF BETA 1104 00:55:57,922 --> 00:55:58,222 SIGNALLING. 1105 00:55:58,222 --> 00:55:58,356 . 1106 00:55:58,356 --> 00:56:02,393 THE HYPOTHESIS OR WHAT WE'RE 1107 00:56:02,393 --> 00:56:08,666 CURRENTLY EVALUATING IS LOOKING 1108 00:56:08,666 --> 00:56:11,369 AT AN EXPRESSION BY CD 8 T CELLS 1109 00:56:11,369 --> 00:56:13,905 AND WE'RE SHOWING THE EXPRESSION 1110 00:56:13,905 --> 00:56:17,609 IS IMPORTANT IN ELITE 1111 00:56:17,609 --> 00:56:22,213 CONTROLLERS IN TERMS OF A 1112 00:56:22,213 --> 00:56:23,581 NON-CYTOLYTIC EXPRESSION AND SO 1113 00:56:23,581 --> 00:56:24,415 CONFIRMED BY OTHER GROUP AND 1114 00:56:24,415 --> 00:56:27,485 ESSENTIALLY BY MODULATING THAT 1115 00:56:27,485 --> 00:56:33,224 PARTICULAR PATHWAY WE'RE SEEING 1116 00:56:33,224 --> 00:56:40,298 UP REGULATION OF TGF BETA AND 1117 00:56:40,298 --> 00:56:44,335 INTERESTED IN AND AS GUIDO 1118 00:56:44,335 --> 00:56:45,403 MENTIONED IN THE NONHUMAN 1119 00:56:45,403 --> 00:56:47,639 PRIMATE WE'VE LOOKED AT THE CD 8 1120 00:56:47,639 --> 00:56:50,375 DEPLETION AND ONE THING WE'RE 1121 00:56:50,375 --> 00:56:54,746 INTERESTED IN IS PARTNERING WITH 1122 00:56:54,746 --> 00:56:58,216 BEING ABLE IT DELIVER MOLECULES 1123 00:56:58,216 --> 00:57:05,623 TO RELEASE REPRESSION TO HAVE CD 1124 00:57:05,623 --> 00:57:07,225 8 T CELLS AND BLOCK THE ROW 1125 00:57:07,225 --> 00:57:09,227 PRESSIVE MECHANISMS. 1126 00:57:09,227 --> 00:57:11,929 WE'RE CURRENTLY DOING STUDIES 1127 00:57:11,929 --> 00:57:13,464 WITH MERCK TO SCREEN FOR 1128 00:57:13,464 --> 00:57:14,198 COMPOUNDS AND DOING LIBRARY 1129 00:57:14,198 --> 00:57:18,102 SCREENS TO LOOK AT PATHWAYS TO 1130 00:57:18,102 --> 00:57:19,303 POTENTIALLY ALSO ALLEVIATE THE 1131 00:57:19,303 --> 00:57:20,271 EXPRESSION MECHANISM IN THE 1132 00:57:20,271 --> 00:57:23,041 PRESENCE OF CD 8s. 1133 00:57:23,041 --> 00:57:24,509 SO WE'RE GOING THROUGH THAT 1134 00:57:24,509 --> 00:57:26,778 SYSTEMATIC APPROACH TO LOOK AT 1135 00:57:26,778 --> 00:57:27,979 DIFFERENT MOLECULES TO BE ABLE 1136 00:57:27,979 --> 00:57:31,182 TO DO THAT WITHOUT THE CD 8 1137 00:57:31,182 --> 00:57:31,783 DEPLET 1138 00:57:31,783 --> 00:57:32,050 DEPLETION. 1139 00:57:32,050 --> 00:57:35,453 >> CD 8 CELLS ARE ONE TYPE OF CD 1140 00:57:35,453 --> 00:57:38,723 8 CELL EFFECTER MEMORY CELL 1141 00:57:38,723 --> 00:57:39,657 OR -- 1142 00:57:39,657 --> 00:57:41,659 >> THAT'S A GOOD QUESTION AND 1143 00:57:41,659 --> 00:57:45,596 WE'RE IDENTIFYING THE CD 8 T 1144 00:57:45,596 --> 00:57:47,131 CELL SUBSET. 1145 00:57:47,131 --> 00:57:49,434 THERE'S CORRELATES IN THE CANCER 1146 00:57:49,434 --> 00:57:50,301 LITERATURE FOR A PARTICULAR T 1147 00:57:50,301 --> 00:57:52,203 CELL SUB POPULATIONS THAT HAVE 1148 00:57:52,203 --> 00:57:53,971 EXPRESSIVE ACTIVITY. 1149 00:57:53,971 --> 00:57:56,574 IN PARTICULAR LIKE FOR EXAMPLE 1150 00:57:56,574 --> 00:57:59,944 KNOWN TO IMPEDE A TUMOR 1151 00:57:59,944 --> 00:58:03,681 INFILTRATION AND WORKING ON 1152 00:58:03,681 --> 00:58:09,253 IMPEDING CYTOLYTIC TARGETS TO 1153 00:58:09,253 --> 00:58:10,388 CREATE THE EXPRESSION MECHANISM 1154 00:58:10,388 --> 00:58:12,690 BY CD 8s. 1155 00:58:12,690 --> 00:58:13,825 WE IDENTIFIED A FEW MARKERS THAT 1156 00:58:13,825 --> 00:58:16,060 SEEM TO BE CRITICAL FOR THE CD 1157 00:58:16,060 --> 00:58:17,995 8s TO HAVE IN ORDER TO PROMOTE 1158 00:58:17,995 --> 00:58:19,330 THE EXPRESSION ACTIVITY. 1159 00:58:19,330 --> 00:58:23,201 SO THE NEXT STEP IS TO BE ABLE 1160 00:58:23,201 --> 00:58:24,168 TO CORRELATE THAT WITH 1161 00:58:24,168 --> 00:58:26,370 EXPRESSION AND LOCALIZATION OF 1162 00:58:26,370 --> 00:58:28,906 THOSE CD 8 T CELLS IN THE 1163 00:58:28,906 --> 00:58:30,408 NONHUMAN PRIMATE MODEL TO BE 1164 00:58:30,408 --> 00:58:32,376 SABLE TO SAY WHERE ARE THE CELLS 1165 00:58:32,376 --> 00:58:34,378 AND WHEN THEY'RE INTERACTING 1166 00:58:34,378 --> 00:58:38,816 WITH THE CD4s AND INFECTION AND 1167 00:58:38,816 --> 00:58:39,717 FOLLOW-UP IN PEOPLE LIVING WITH 1168 00:58:39,717 --> 00:58:47,191 HIV AND THOSE CELLS. 1169 00:58:47,191 --> 00:58:51,562 >> AND THE REFERENCE TO JAY WAS 1170 00:58:51,562 --> 00:58:53,731 IMPORTANT BECAUSE HE WAS AN 1171 00:58:53,731 --> 00:58:55,566 INFLUENTIAL SCIENTIST FOR A LOT 1172 00:58:55,566 --> 00:58:57,301 OF US A PERSONAL FRIEND AND 1173 00:58:57,301 --> 00:58:59,604 ESTEEMED COLLEAGUE AND 1174 00:58:59,604 --> 00:58:59,904 EVERYTHING. 1175 00:58:59,904 --> 00:59:03,274 SO JAY LEEVY FAILED TO IDENTIFY 1176 00:59:03,274 --> 00:59:04,842 THE FACTOR AND I THINK IT'S 1177 00:59:04,842 --> 00:59:10,381 IMPORTANT WITH THE GROUP TO 1178 00:59:10,381 --> 00:59:12,116 DISCUSS AND WE DIDN'T HAVE THE 1179 00:59:12,116 --> 00:59:17,088 TECHNOLOGY WE HAVE NOW. 1180 00:59:17,088 --> 00:59:18,756 AND THE REASON NUMBER 2 I THINK 1181 00:59:18,756 --> 00:59:21,993 JAY GOT REALLY CONFUSED AND 1182 00:59:21,993 --> 00:59:24,762 STUCK IN THIS DICHOTOMY BETWEEN 1183 00:59:24,762 --> 00:59:25,296 SOLUBLE AND CELL TO CELL 1184 00:59:25,296 --> 00:59:33,738 CONTACT. 1185 00:59:33,738 --> 00:59:34,405 . 1186 00:59:34,405 --> 00:59:34,539 . 1187 00:59:34,539 --> 00:59:37,074 AND IT HAPPENED WHEN THE CELLS 1188 00:59:37,074 --> 00:59:38,409 ARE CLOSED. 1189 00:59:38,409 --> 00:59:40,912 WE GOT CAUGHT INTO THIS IS THIS 1190 00:59:40,912 --> 00:59:43,214 A SOLUBLE FACTOR BUT IN FACT 1191 00:59:43,214 --> 00:59:45,383 IT'S SOMETHING IN BETWEEN. 1192 00:59:45,383 --> 00:59:48,419 AND POINT NUMBER 3 IS THE OLDER 1193 00:59:48,419 --> 00:59:50,288 FOLKS IN THE ROOM WILL REMEMBER, 1194 00:59:50,288 --> 00:59:53,758 JAY THOUGHT THAT WAS THE REASON 1195 00:59:53,758 --> 00:59:57,161 THE LONG-TERM NON-PROGRESSERS 1196 00:59:57,161 --> 01:00:01,165 REMAINED LOW VIREMIC AND KNOW 1197 01:00:01,165 --> 01:00:04,235 THE EFFECT IS ALSO IN DONORS 1198 01:00:04,235 --> 01:00:05,102 THAT NEVER RECEIVED HIV AND A 1199 01:00:05,102 --> 01:00:07,038 LOT OF THIS IS RELATED TO THE 1200 01:00:07,038 --> 01:00:08,105 TECHNOLOGY THAT WASN'T AVAILABLE 1201 01:00:08,105 --> 01:00:09,373 AT THE TIME. 1202 01:00:09,373 --> 01:00:12,643 AND THE WHOLE THING STOPPED AND 1203 01:00:12,643 --> 01:00:14,779 WE WERE LUCKY TO RESURRECT IT. 1204 01:00:14,779 --> 01:00:18,082 ONCE YOU DEPLETE THE CD 8 IN 1205 01:00:18,082 --> 01:00:20,852 VIVO THERE'S A BIG REBOUND OF 1206 01:00:20,852 --> 01:00:23,321 VIREMIA SEEN IN 40 DIFFERENT 1207 01:00:23,321 --> 01:00:23,554 ANIMALS. 1208 01:00:23,554 --> 01:00:25,623 50 WHATEVER THE NUMBER IS. 1209 01:00:25,623 --> 01:00:29,694 >> I DIDN'T MEAN TO BE CRITICAL. 1210 01:00:29,694 --> 01:00:31,762 NOT AT ALL BUT THINGS HAPPENED A 1211 01:00:31,762 --> 01:00:35,466 LONG TIME AGO AND YOU KNOW. 1212 01:00:35,466 --> 01:00:36,601 >> WE CAN CONTINUE THE 1213 01:00:36,601 --> 01:00:40,738 DISCUSSION AT THE COFFEE BREAK. 1214 01:00:40,738 --> 01:00:42,139 >> THERE'S A QUESTION AND 1215 01:00:42,139 --> 01:00:43,908 CURIOUS ON THE GENETIC DATA ONE 1216 01:00:43,908 --> 01:00:46,110 THING THAT STOOD OUT TO ME WAS 1217 01:00:46,110 --> 01:00:48,045 IT SEEMED TO BE OPPOSITE TO 1218 01:00:48,045 --> 01:00:49,447 EVERYTHING ELSE GOING ON. 1219 01:00:49,447 --> 01:00:51,015 WONDERING IF YOU CAN COMMENT ON 1220 01:00:51,015 --> 01:00:51,215 THAT. 1221 01:00:51,215 --> 01:00:52,917 >> SO YEAH THERE'S A LOT OF 1222 01:00:52,917 --> 01:00:54,051 PATHWAYS WE HAVEN'T HAD A CHANCE 1223 01:00:54,051 --> 01:00:56,420 NO GET TO YET AND THAT'S ONE AND 1224 01:00:56,420 --> 01:00:57,588 STAT SIGNALLING IS ONE THAT 1225 01:00:57,588 --> 01:00:59,423 WE'RE VERY INTERESTED IN FOR A 1226 01:00:59,423 --> 01:01:04,896 LOT OF DIFFERENT MECHANISMS SO 1227 01:01:04,896 --> 01:01:06,931 ABSOLUTELY WILL FOLLOW-UP. 1228 01:01:06,931 --> 01:01:11,702 >> THIS IS FROM THE OVERFLOW 1229 01:01:11,702 --> 01:01:11,903 ROOM. 1230 01:01:11,903 --> 01:01:15,473 INTERESTING DATA ON THE DELIVERY 1231 01:01:15,473 --> 01:01:18,976 BY LNPs WHERE DO YOU THINK THE 1232 01:01:18,976 --> 01:01:20,778 CELLS WILL HOME TO NOW THAT YOUR 1233 01:01:20,778 --> 01:01:22,213 OVER EXPRESSION THE RECEPTOR AND 1234 01:01:22,213 --> 01:01:22,813 WHERE DO THEY TRAFFIC IN THE 1235 01:01:22,813 --> 01:01:25,016 MICE? 1236 01:01:25,016 --> 01:01:35,559 >> IN MICE WE'VE ONLY USED THE 1237 01:01:38,362 --> 01:01:41,465 GFP AND DIDN'T SEE TRAFFICKING 1238 01:01:41,465 --> 01:01:42,166 OF THE CELLS IN THE LYMPH NODES 1239 01:01:42,166 --> 01:01:44,201 PAUSE THEY DON'T HAVE THE HOMING 1240 01:01:44,201 --> 01:01:46,203 RECEPTORS. 1241 01:01:46,203 --> 01:01:52,810 OF COURSE ONCE WE DELIVER 60CD2L 1242 01:01:52,810 --> 01:01:55,579 WE HOPE THEY'LL BE ABLE TO ENTER 1243 01:01:55,579 --> 01:01:57,882 THE LYMPH NODES. 1244 01:01:57,882 --> 01:02:01,085 WE MAY NEED TO EXPRESS CD R7 AS 1245 01:02:01,085 --> 01:02:06,557 WELL BUT KNOW FROM PREVIOUS 1246 01:02:06,557 --> 01:02:08,426 LITERATURE FROM WAY BACK WHEN 1247 01:02:08,426 --> 01:02:11,862 AND IN COLLABORATION WITH TED 1248 01:02:11,862 --> 01:02:14,098 JUST EXPRESSION IT TOPICALLY IN 1249 01:02:14,098 --> 01:02:22,773 MICE ON ESSENTIALLY ALL CD 8 T 1250 01:02:22,773 --> 01:02:24,775 CELLS ALLOWS CONTINUAL ENTRY 1251 01:02:24,775 --> 01:02:30,348 INTO THE LYMPH NODE. 1252 01:02:30,348 --> 01:02:31,816 >> ALL RIGHT. 1253 01:02:31,816 --> 01:02:38,356 I'D LIKE TO INVITE THE CARE 1254 01:02:38,356 --> 01:02:39,757 SPEAKERS AND WHILE THEY'RE 1255 01:02:39,757 --> 01:02:41,792 APPROACHING THE STAGE REMINDER 1256 01:02:41,792 --> 01:02:46,197 IF YOU PLAN TO GET LUNCH ORDER 1257 01:02:46,197 --> 01:02:46,964 THROUGH CHOPPED YOU HAVE ABOUT 1258 01:02:46,964 --> 01:02:49,600 10 MORE MINUTES TO DO THAT MAYBE 1259 01:02:49,600 --> 01:02:50,768 A LITTLE BIT LESS. 1260 01:02:50,768 --> 01:02:56,841 9:45 IS THE ONLINE CUT OFF FOR 1261 01:02:56,841 --> 01:03:00,811 CHOPPED DROP THE WEBSITE AND QR 1262 01:03:00,811 --> 01:03:04,015 CODE IS OUTSIDE AT THE MAIN 1263 01:03:04,015 --> 01:03:04,382 DESK. 1264 01:03:04,382 --> 01:03:06,150 THIS IS THE FINAL COLLABORATORY 1265 01:03:06,150 --> 01:03:10,287 PRESENTATION SO IMMEDIATELY 1266 01:03:10,287 --> 01:03:11,522 FOLLOWING THIS SESSION WE'LL 1267 01:03:11,522 --> 01:03:13,391 BREAK UNTIL 11:00 AND HAVE TWO 1268 01:03:13,391 --> 01:03:14,125 PANEL DISCUSSION. 1269 01:03:14,125 --> 01:03:15,393 WE'RE LOOKING FORWARD TO THAT. 1270 01:03:15,393 --> 01:03:16,160 I HOPE YOU CAN STAY AROUND FOR 1271 01:03:16,160 --> 01:03:24,802 THOSE DISCUSSIONS. 1272 01:03:24,802 --> 01:03:27,238 THIS IS THE THIRD ITERATION OF 1273 01:03:27,238 --> 01:03:33,878 THE CARE GROUP LED BY THE 1274 01:03:33,878 --> 01:03:41,652 UNIVERSITY NORTH CAROLINA CHAPEL 1275 01:03:41,652 --> 01:03:41,852 HILL. 1276 01:03:41,852 --> 01:03:43,287 >> THANKS TO THOSE IN THE ROOM 1277 01:03:43,287 --> 01:03:44,355 REMAINING TO THE END. 1278 01:03:44,355 --> 01:03:44,922 I'M PRETTY TIRED. 1279 01:03:44,922 --> 01:03:46,690 I HOPE I CAN DO MY JOB. 1280 01:03:46,690 --> 01:03:48,692 I WOULD LIKE TO FIRST THANK ALL 1281 01:03:48,692 --> 01:03:50,361 THE INVESTIGATORS IN CARE. 1282 01:03:50,361 --> 01:03:51,862 UNFORTUNATELY WE WON'T HAVE TIME 1283 01:03:51,862 --> 01:03:53,798 TO PRESENT EVERYONE'S WORK 1284 01:03:53,798 --> 01:03:54,398 TODAY. 1285 01:03:54,398 --> 01:03:59,203 I'M JUST GOING TO TRY TO GIVE AN 1286 01:03:59,203 --> 01:04:03,808 OVERVIEW OF WHERE WE'RE GOING 1287 01:04:03,808 --> 01:04:07,311 WITH HIGHLIGHTS TO DELVE INTO IN 1288 01:04:07,311 --> 01:04:08,079 MORE DETAIL. 1289 01:04:08,079 --> 01:04:09,713 I DON'T NEED TO TALK ABOUT THE 1290 01:04:09,713 --> 01:04:10,214 SLIDE. 1291 01:04:10,214 --> 01:04:12,883 IT'S THE OVER ALL CONCEPTUAL 1292 01:04:12,883 --> 01:04:13,150 IDEA. 1293 01:04:13,150 --> 01:04:15,786 AS WE TALKED ABOUT OTHER 1294 01:04:15,786 --> 01:04:22,026 APPROACHES AND OTHER IDEAS OVER 1295 01:04:22,026 --> 01:04:24,361 THE MEETING AND WE'RE 1296 01:04:24,361 --> 01:04:25,162 INCORPORATING ADVANCES AND 1297 01:04:25,162 --> 01:04:27,264 PERHAPS THE FUTURE WILL LOOK 1298 01:04:27,264 --> 01:04:29,600 SOMEWHAT DIFFERENT THAN THIS BUT 1299 01:04:29,600 --> 01:04:31,402 THIS IS WHAT WE'VE BEEN MOVING 1300 01:04:31,402 --> 01:04:40,644 TOWARDS. 1301 01:04:40,644 --> 01:04:42,513 I WANTED TO START WITH OUR 1302 01:04:42,513 --> 01:04:44,014 EFFORTS WITH THE COMMUNITY. 1303 01:04:44,014 --> 01:04:48,953 WE HAVE THREE COMMUNITY PARTNERS 1304 01:04:48,953 --> 01:04:50,387 AND THE CARE GROUP THE COMMUNITY 1305 01:04:50,387 --> 01:04:53,491 ADVISORY BOARD OF CARE AND 1306 01:04:53,491 --> 01:04:54,525 OTHERS HAVE COLLABORATED WITH 1307 01:04:54,525 --> 01:04:59,096 THESE PARTNERS AS YOU CAN SEE 1308 01:04:59,096 --> 01:05:00,064 APPEARING AT THEIR VARIOUS 1309 01:05:00,064 --> 01:05:03,701 EVENTS AND BRINGING THE IDEA OF 1310 01:05:03,701 --> 01:05:06,036 CARE AND CURE RESEARCH INTO OUR 1311 01:05:06,036 --> 01:05:06,303 COMMUNITY. 1312 01:05:06,303 --> 01:05:09,840 I THINK UNLIKE MANY OF THE 1313 01:05:09,840 --> 01:05:12,076 COLLABORATORY LOCATIONS, WE ARE 1314 01:05:12,076 --> 01:05:16,580 MOSTLY IN PART OF THE SOUTHEAST 1315 01:05:16,580 --> 01:05:18,916 HIV EPIDEMIC IN THE U.S. WHICH 1316 01:05:18,916 --> 01:05:20,518 IS DIFFERENT POPULATIONS. 1317 01:05:20,518 --> 01:05:22,419 WE HAVE SORT OF CITIES BUT NOT 1318 01:05:22,419 --> 01:05:25,389 BIG CITIES. 1319 01:05:25,389 --> 01:05:26,857 PEOPLE COME FROM DISTANCES AND 1320 01:05:26,857 --> 01:05:28,626 THE SETTING IS PRETTY DIFFERENT 1321 01:05:28,626 --> 01:05:29,860 THAN A LOT OF OTHER PLACES WHERE 1322 01:05:29,860 --> 01:05:32,530 CURE RESEARCH IS GOING ON. 1323 01:05:32,530 --> 01:05:35,399 IN ADDITION TO WORKING WITH 1324 01:05:35,399 --> 01:05:37,968 THESE GROUPS, WE'VE ALSO GONE 1325 01:05:37,968 --> 01:05:41,172 OUT INTO VARIOUS RELEVANT 1326 01:05:41,172 --> 01:05:45,809 COMMUNITY EVENTS AND INTERACTED 1327 01:05:45,809 --> 01:05:51,282 WITH PEOPLE DEVELOPING BOTH WHAT 1328 01:05:51,282 --> 01:05:53,417 WE INVITED THE COMMUNITY TO AND 1329 01:05:53,417 --> 01:05:56,253 INFORMATION AND BROCHURES WE'RE 1330 01:05:56,253 --> 01:05:59,657 NOW USING TO HELP US INTERACT 1331 01:05:59,657 --> 01:06:02,293 AND BRING THIS INFORMATION 1332 01:06:02,293 --> 01:06:02,526 FORWARD. 1333 01:06:02,526 --> 01:06:05,462 FOR THIS COMING YEAR WE HAVE AN 1334 01:06:05,462 --> 01:06:08,165 UPCOMING EVENT AT THE GOVERNOR'S 1335 01:06:08,165 --> 01:06:16,674 MANSION AND THE GROUP HAS SPENT 1336 01:06:16,674 --> 01:06:17,841 TIME LOOKING AT WHAT WE ARE 1337 01:06:17,841 --> 01:06:20,110 DOING AND HOW WE'RE DOING IT TO 1338 01:06:20,110 --> 01:06:21,845 EVALUATE HOW WE CAN BE IMPACTFUL 1339 01:06:21,845 --> 01:06:23,547 IN THE DIFFERENT COMMUNITIES WE 1340 01:06:23,547 --> 01:06:33,891 SERVE GOING FORWARD. 1341 01:06:37,328 --> 01:06:40,564 I LOOK FORWARD TO ENACTING WITH 1342 01:06:40,564 --> 01:06:41,799 OTHER COMMUNITY MEMBERS AND 1343 01:06:41,799 --> 01:06:43,200 LOOKING AT THE BIOLOGY OF 1344 01:06:43,200 --> 01:06:45,669 LATENCY TO INFORM US HOW TO MOVE 1345 01:06:45,669 --> 01:06:47,805 FORWARD INTO PEOPLE WITH THIS 1346 01:06:47,805 --> 01:06:52,676 INFORMATION TO DEVELOP 1347 01:06:52,676 --> 01:06:56,714 THERAPEUTIC STRATEGIES. 1348 01:06:56,714 --> 01:07:01,852 AND ONE WITH A GROUP AND OTHERS 1349 01:07:01,852 --> 01:07:03,487 AND I'M SURE YOU'RE WELL AWARE 1350 01:07:03,487 --> 01:07:09,460 OF IS THIS IDEA WHILE VIREMIA IS 1351 01:07:09,460 --> 01:07:11,028 DIFFERENT THROUGH THE COURSE OF 1352 01:07:11,028 --> 01:07:13,030 INFECTION THE VIRUSES THAT END 1353 01:07:13,030 --> 01:07:16,033 UP IN THE RESERVOIR APPEAR IN 1354 01:07:16,033 --> 01:07:24,441 MOST PEOPLE TO MOSTLY EMANATE 1355 01:07:24,441 --> 01:07:26,377 FROM EXPANSION AND YOU CAN SEE 1356 01:07:26,377 --> 01:07:28,979 WHILE SOME OF THE OLD VIRUSES IN 1357 01:07:28,979 --> 01:07:33,517 RED OR OTHER COLORS ARE IN THE 1358 01:07:33,517 --> 01:07:34,418 RESERVOIR IN SOME PEOPLE MOST 1359 01:07:34,418 --> 01:07:36,520 THE VIRUSES IN MOST PEOPLE COME 1360 01:07:36,520 --> 01:07:39,256 FROM MORE RECENTLY CIRCULATING 1361 01:07:39,256 --> 01:07:40,591 VIRUSES WITHIN THE LAST YEAR 1362 01:07:40,591 --> 01:07:47,097 PRIOR TO ART INITIATION. 1363 01:07:47,097 --> 01:07:51,535 SO WHERE PEOPLE WERE BASHING ON 1364 01:07:51,535 --> 01:07:52,636 INFECTION AND DURABLE EXPRESSION 1365 01:07:52,636 --> 01:07:54,905 THIS OFFERED A NEW WINDOW TO 1366 01:07:54,905 --> 01:07:56,740 ATTACK THE RESERVOIR EARLY AT 1367 01:07:56,740 --> 01:07:59,743 THE INITIATION OF ART. 1368 01:07:59,743 --> 01:08:03,681 YOU CAN SEE IT MOVE FORWARD WITH 1369 01:08:03,681 --> 01:08:07,951 MULTIPLE STUDY SOME OF WHICH 1370 01:08:07,951 --> 01:08:09,086 WERE DISCUSSED IN THE 1371 01:08:09,086 --> 01:08:11,155 PRESENTATION OTHERS DONE IN 1372 01:08:11,155 --> 01:08:11,789 CARE. 1373 01:08:11,789 --> 01:08:14,391 SARA WILL HAVE DATA SOON FROM 10 1374 01:08:14,391 --> 01:08:17,861 WOMEN IN THE COHORT WHO FOR 1375 01:08:17,861 --> 01:08:18,929 VARIOUS REASONS INTERRUPTED ART 1376 01:08:18,929 --> 01:08:20,931 AND WE'LL SEE WHERE THE REBOUND 1377 01:08:20,931 --> 01:08:22,833 VIRUSES COME FROM IF THEY COME 1378 01:08:22,833 --> 01:08:25,736 FROM THE MORE RECENT OR MOVE 1379 01:08:25,736 --> 01:08:28,872 DISTANT RESERVOIR OR SOME MIX. 1380 01:08:28,872 --> 01:08:37,448 FURTHER, SOME OBSERVATIONS 1381 01:08:37,448 --> 01:08:38,916 SUGGESTS THE PRESENCE OF THE 1382 01:08:38,916 --> 01:08:40,684 INHIBITOR MAY IMPEDE THE 1383 01:08:40,684 --> 01:08:41,785 DEVELOPMENT OF THE RESERVOIR. 1384 01:08:41,785 --> 01:08:44,121 SO JUMPING OVER THE ANIMAL 1385 01:08:44,121 --> 01:08:47,291 MODELS WE WERE ABLE TO GO TO THE 1386 01:08:47,291 --> 01:08:50,094 ACTG AND DEVELOP A PILOT HUMAN 1387 01:08:50,094 --> 01:08:51,128 CLINICAL TRIAL STILL IN 1388 01:08:51,128 --> 01:08:54,698 DEVELOPMENT BUT SLATED TO 1389 01:08:54,698 --> 01:08:58,402 POTENTIALLY OPEN THIS COMING 1390 01:08:58,402 --> 01:09:03,207 YEAR INTERNATIONALLY. 1391 01:09:03,207 --> 01:09:11,815 A LARGE GROUP LOOKING AT HIV 1392 01:09:11,815 --> 01:09:12,516 PERSISTENCE IN TISSUE. 1393 01:09:12,516 --> 01:09:17,955 THE MERCK GROUP HAS CONTRIBUTED 1394 01:09:17,955 --> 01:09:19,423 SIGNIFICANTLY TO THIS AND I'LL 1395 01:09:19,423 --> 01:09:24,728 SHOW OTHER PIECES OF DATA AS AN 1396 01:09:24,728 --> 01:09:26,397 OVERVIEW. 1397 01:09:26,397 --> 01:09:31,301 THIS IS WORK FROM NADIA ROME YOU 1398 01:09:31,301 --> 01:09:33,937 HEARD SOME OF HER OTHER WORK 1399 01:09:33,937 --> 01:09:35,372 THIS WEEK AND HER HIV PREPS 1400 01:09:35,372 --> 01:09:40,944 ASSAY ABLE TO DETECT THE mRNA 1401 01:09:40,944 --> 01:09:44,648 CELLS BY SEQ AND SHOW MOST BUT 1402 01:09:44,648 --> 01:09:47,818 NOT ALL CELLS ARE POSITIVE FOR 1403 01:09:47,818 --> 01:09:51,722 THE ANTIGEN. 1404 01:09:51,722 --> 01:09:53,824 GUIDO FERRARI'S GROUP AT DUKE 1405 01:09:53,824 --> 01:09:56,126 HAS BEEN ABLE TO ACCESS TISSUE 1406 01:09:56,126 --> 01:09:58,061 FROM THE HOPE TRANSPLANT 1407 01:09:58,061 --> 01:09:58,295 PROGRAM. 1408 01:09:58,295 --> 01:10:02,032 IT'S A PROGRAM OF HIV POSITIVE 1409 01:10:02,032 --> 01:10:04,368 DONORS FOR HIV POSITIVE 1410 01:10:04,368 --> 01:10:04,668 TRANSPLANTS. 1411 01:10:04,668 --> 01:10:06,069 A TRANSPLANT FOR INSTANCE WHEN A 1412 01:10:06,069 --> 01:10:09,540 KIDNEY IS REMOVED, LOCAL LYMPH 1413 01:10:09,540 --> 01:10:10,674 NODES ARE AVAILABLE AND HE'S 1414 01:10:10,674 --> 01:10:20,651 BEEN ABLE TO ACQUIRE ALL LYMPH 1415 01:10:20,651 --> 01:10:31,195 NODES FROM PEOPLE EXPRESSED AND 1416 01:10:32,229 --> 01:10:33,630 SEE WIDE VARIETY OF CELLS 1417 01:10:33,630 --> 01:10:35,165 CHANGED BY THE EXPOSURE. 1418 01:10:35,165 --> 01:10:38,602 THIS IS ALSO ILLUSTRATED IN THIS 1419 01:10:38,602 --> 01:10:40,471 FIGURE IN A DIFFERENT WAY 1420 01:10:40,471 --> 01:10:42,139 SHOWING BEFORE AND AFTER IN THE 1421 01:10:42,139 --> 01:10:45,542 DIFFERENT POPULATIONS IN THE 1422 01:10:45,542 --> 01:10:47,077 PRESENCE OF SEVERAL DIFFERENT 1423 01:10:47,077 --> 01:10:50,380 ART, LOVE RA COMBINATIONS. 1424 01:10:50,380 --> 01:10:51,615 INTERESTINGLY -- LRA 1425 01:10:51,615 --> 01:10:51,915 COMBINATION. 1426 01:10:51,915 --> 01:10:55,519 WHEN YOU LOOK AT THE CELLS THAT 1427 01:10:55,519 --> 01:10:58,989 BECOME POSITIVE FOR RNA IN THE 1428 01:10:58,989 --> 01:11:05,128 EXPERIMENT YOU SEE MOST OF THESE 1429 01:11:05,128 --> 01:11:08,398 CELLS HAVE A TFH AND THAT IS AN 1430 01:11:08,398 --> 01:11:09,666 OBSERVATION THAT CAN BE 1431 01:11:09,666 --> 01:11:12,236 REFLECTED ON OTHER STUDIES 1432 01:11:12,236 --> 01:11:13,170 EARLIER IN THE WEEK THAT NEEDS 1433 01:11:13,170 --> 01:11:17,407 FURTHER DEVELOPMENT. 1434 01:11:17,407 --> 01:11:18,375 LAST YEAR COLLABORATORS 1435 01:11:18,375 --> 01:11:20,577 INCLUDING VERY IMPORTANTLY THE 1436 01:11:20,577 --> 01:11:26,383 LAST GIFT COHORT SHOWED 1437 01:11:26,383 --> 01:11:36,693 DEFINITIVELY THE MICROGLIA SHOW 1438 01:11:36,693 --> 01:11:41,832 THEIR CLEARLY DIFFERENT THAN LRA 1439 01:11:41,832 --> 01:11:43,467 RESPONSES IN T CELLS AND SOME 1440 01:11:43,467 --> 01:11:45,335 OBSERVATIONS WILL BE COMING OUT 1441 01:11:45,335 --> 01:11:45,936 IN THE LITERATURE RELATIVELY 1442 01:11:45,936 --> 01:11:48,906 SOON. 1443 01:11:48,906 --> 01:11:52,276 THE LAST PART OF THE BIOLOGY OF 1444 01:11:52,276 --> 01:11:54,111 LATENCY LOOKS DIRECTLY AT THE 1445 01:11:54,111 --> 01:12:01,318 DEVELOPMENT OF LRAs. 1446 01:12:01,318 --> 01:12:05,255 AS YOU KNOW WE RESERVED LATENCY 1447 01:12:05,255 --> 01:12:07,257 SOME TIME AGO AND WE CONTINUED 1448 01:12:07,257 --> 01:12:09,293 TO WORK IN DIFFERENT AREAS 1449 01:12:09,293 --> 01:12:12,396 DEVELOPING NEW LRAs PARTICULARLY 1450 01:12:12,396 --> 01:12:17,834 THOSE THAT MIGHT SYNERGIZE WITH 1451 01:12:17,834 --> 01:12:18,769 PREVIOUSLY DESCRIBED ONES. 1452 01:12:18,769 --> 01:12:20,604 SOME WORK I DON'T HAVE TIME TO 1453 01:12:20,604 --> 01:12:22,272 PRESENT HERE, CAT PRESENTED HER 1454 01:12:22,272 --> 01:12:26,677 POSTER YESTERDAY AND YOU GOT TO 1455 01:12:26,677 --> 01:12:30,013 SEE THAT AND IMPORTANTLY THERE 1456 01:12:30,013 --> 01:12:35,819 WAS A CRISPR SCREEN LOOKING FOR 1457 01:12:35,819 --> 01:12:41,725 LRA TARGETS FOR THOSE THAT MIGHT 1458 01:12:41,725 --> 01:12:45,762 SYNERGIZE WITH NON-CANONICAL 1459 01:12:45,762 --> 01:12:46,063 SIGNALLING. 1460 01:12:46,063 --> 01:12:48,532 THE NEXT PART IS DEVELOPING 1461 01:12:48,532 --> 01:12:51,768 IMMUNE MODULATION APPROACHES OR 1462 01:12:51,768 --> 01:12:52,402 IMMUNOTHERAPIES TO CONTROL VIRAL 1463 01:12:52,402 --> 01:13:00,043 REBOUND. 1464 01:13:00,043 --> 01:13:02,245 ONE EFFORT THAT'S GONE ON IS THE 1465 01:13:02,245 --> 01:13:05,282 DELIVERY OF INHIBITERS BY AAV 1466 01:13:05,282 --> 01:13:09,853 LED BY MATT GARNER AND MICHAEL 1467 01:13:09,853 --> 01:13:10,420 FARSAN. 1468 01:13:10,420 --> 01:13:12,889 ORIGINALLY THIS WAS MOSTLY 1469 01:13:12,889 --> 01:13:14,925 LOOKING AT DELIVERY OF ECA4 1470 01:13:14,925 --> 01:13:17,861 WRAPPED YOU WORK IN PAVE WITH 1471 01:13:17,861 --> 01:13:20,130 THE VECTORS. 1472 01:13:20,130 --> 01:13:22,132 THE VECTORS ARE BEING IMPROVED 1473 01:13:22,132 --> 01:13:22,799 AND DEVELOPED FOR FUTURE ANIMAL 1474 01:13:22,799 --> 01:13:29,539 EXPERIMENTS. 1475 01:13:29,539 --> 01:13:32,843 ANOTHER MAJOR ADVANCE IS THE 1476 01:13:32,843 --> 01:13:35,612 IDEA OF DEVELOPING WAYS TO 1477 01:13:35,612 --> 01:13:38,115 TARGET HIV INFECTED CELLS 1478 01:13:38,115 --> 01:13:40,050 PRESENTING ON THE PEP SIDE IN 1479 01:13:40,050 --> 01:13:41,418 THE HLE COMPLEX. 1480 01:13:41,418 --> 01:13:44,655 THIS IS A VERY COMPLEX IDEA. 1481 01:13:44,655 --> 01:13:47,624 IT'S GOING TO BE BEAUTIFULLY 1482 01:13:47,624 --> 01:13:48,692 EXPLAINED IN A PRESENTATION 1483 01:13:48,692 --> 01:13:48,992 SHORTLY. 1484 01:13:48,992 --> 01:13:49,926 SO I WON'T DO A BAD JOB OF 1485 01:13:49,926 --> 01:13:55,065 TRYING TO DO THAT. 1486 01:13:55,065 --> 01:13:56,533 AND THEN FINALLY THIS STEP 1487 01:13:56,533 --> 01:13:57,934 BEFORE GOING INTO HUMAN STUDIES 1488 01:13:57,934 --> 01:14:00,470 IS THE WORK IN THE ANIMAL 1489 01:14:00,470 --> 01:14:01,271 MODELS. 1490 01:14:01,271 --> 01:14:04,975 WE'VE CONTINUED TO ITERATIVELY 1491 01:14:04,975 --> 01:14:07,110 STUDY WORK IN HUMANIZED MOUSE 1492 01:14:07,110 --> 01:14:08,612 MODEL AND PRIMATE AND GUIDO IS 1493 01:14:08,612 --> 01:14:10,247 GOING TO GO THROUGH MANY OF 1494 01:14:10,247 --> 01:14:12,382 THOSE RECENT STUDIES. 1495 01:14:12,382 --> 01:14:19,256 SO NOW WE'LL MOVE TO CARLEY. 1496 01:14:19,256 --> 01:14:22,392 THANKS VERY MUCH. 1497 01:14:29,099 --> 01:14:29,266 6: 1498 01:14:29,266 --> 01:14:32,936 >> HI, EVERYONE. 1499 01:14:32,936 --> 01:14:35,305 I'M A Ph.D. GRAD AND I'LL 1500 01:14:35,305 --> 01:14:37,374 PRESENT MY WORK DONE IN 1501 01:14:37,374 --> 01:14:38,475 COLLABORATION WITH CARE. 1502 01:14:38,475 --> 01:14:41,545 ONE OF OUR GOALS IS IMPROVING 1503 01:14:41,545 --> 01:14:42,813 LATENCY REVERSAL FOR HIV CURE 1504 01:14:42,813 --> 01:14:43,847 AND THE SHOCK SIDE OF THE SHOCK 1505 01:14:43,847 --> 01:14:45,148 AND KILL APPROACH. 1506 01:14:45,148 --> 01:14:47,884 SO TO DO THIS WE WOULD FIRSTLY 1507 01:14:47,884 --> 01:14:51,154 LIKE TO IMPROVE UPON EXISTING 1508 01:14:51,154 --> 01:14:54,257 REVERSAL LATENCY AGENT BY 1509 01:14:54,257 --> 01:14:55,459 CONTROLLING LATENCY. 1510 01:14:55,459 --> 01:14:58,395 SECONDLY WE WOULD LIKE TO 1511 01:14:58,395 --> 01:15:01,131 INCREASE POTENCY AND SPECIFICITY 1512 01:15:01,131 --> 01:15:04,901 OF REVERSAL AND IDENTIFY 1513 01:15:04,901 --> 01:15:06,737 DRUGGABLE TARGETS. 1514 01:15:06,737 --> 01:15:10,373 AND SO WE HAVE SEVERAL LATENCY 1515 01:15:10,373 --> 01:15:18,682 REVERSAL AGENT TO REACTIVATE 1516 01:15:18,682 --> 01:15:21,318 CELLS BUT THEY LACK SPECIFICITY 1517 01:15:21,318 --> 01:15:22,853 AND LACK THE RESERVOIR. 1518 01:15:22,853 --> 01:15:25,655 SO ONE STRATEGY BEEN TO PAIR 1519 01:15:25,655 --> 01:15:28,992 DIFFERENT LRAs WITH DIFFERENT 1520 01:15:28,992 --> 01:15:32,295 MECHANISM OF ACTION THAT 1521 01:15:32,295 --> 01:15:34,731 UPREGULATED THE NON-CANONICAL 1522 01:15:34,731 --> 01:15:38,068 PATHWAY AND ONE THAT INCREASES 1523 01:15:38,068 --> 01:15:43,640 THE AVAILABLE PFT. 1524 01:15:43,640 --> 01:15:44,841 AND WE SEE SYNERGY REVERSAL. 1525 01:15:44,841 --> 01:15:47,210 THE COMBINATION WAS BROUGHT INTO 1526 01:15:47,210 --> 01:15:49,946 AN EX VIVO SYSTEM WHERE CELLS OF 1527 01:15:49,946 --> 01:15:54,251 PEOPLE TAKING WIN HIV WERE 1528 01:15:54,251 --> 01:15:56,386 REACTIVATED AND THERE WAS AN 1529 01:15:56,386 --> 01:15:57,521 ADDITIONAL ELONGATION BLOCK. 1530 01:15:57,521 --> 01:15:59,422 WHERE WE CAN UNDERSTAND HOW THE 1531 01:15:59,422 --> 01:16:01,258 LRAs ARE WORKING ON THEIR OWN 1532 01:16:01,258 --> 01:16:02,092 AND TOGETHER THERE'S STILL 1533 01:16:02,092 --> 01:16:07,063 BLOCKS WE CANNOT PREDICT AND SO 1534 01:16:07,063 --> 01:16:10,066 THE EMMERMAN LAB SOUGHT A WAY TO 1535 01:16:10,066 --> 01:16:11,101 ACTIVATE THE BLOCKS. 1536 01:16:11,101 --> 01:16:13,236 TODAY I'LL TELL THE STORY OF 1537 01:16:13,236 --> 01:16:17,874 IMPROVING ON THE ACD AND LRA 1538 01:16:17,874 --> 01:16:24,314 COMBINATION SPECIFICALLY. 1539 01:16:24,314 --> 01:16:32,722 WE USE A CRISPR SCREEN TO 1540 01:16:32,722 --> 01:16:35,225 REACTIVATE AND CAN INTRODUCE A 1541 01:16:35,225 --> 01:16:37,561 LIBRARY OF KNOCKOUTS WITH THE 1542 01:16:37,561 --> 01:16:40,363 HIV CRISPR VECTOR TO TARGET THE 1543 01:16:40,363 --> 01:16:42,833 HIV LATENCY FACTOR SO THE UP 1544 01:16:42,833 --> 01:16:46,837 TERM PROVIRUS IS ACTIVATE AND 1545 01:16:46,837 --> 01:16:49,773 BECAUSE HOW THE VECTOR WAS 1546 01:16:49,773 --> 01:16:52,976 DESIGN WITH THE HIV LTRs IT TOO 1547 01:16:52,976 --> 01:16:57,747 IS REACTIVATED AND PACKAGED SO 1548 01:16:57,747 --> 01:16:59,683 IT ACCUMULATES AND THIS IS A 1549 01:16:59,683 --> 01:17:01,852 STRATEGY TO CLEARLY LINK THE 1550 01:17:01,852 --> 01:17:04,020 KNOCKOUT TO THE REACTIVATION 1551 01:17:04,020 --> 01:17:05,522 PHENOTYPE AND THERE'S LITTLE 1552 01:17:05,522 --> 01:17:06,523 BACKGROUND IN THE SYSTEM. 1553 01:17:06,523 --> 01:17:09,392 AND BY SEQUENCING THE VIRAL 1554 01:17:09,392 --> 01:17:10,627 SUPER NATE ENT IN THE CELLS WE 1555 01:17:10,627 --> 01:17:13,163 CAN USE THE RATIO OF THE GUIDES 1556 01:17:13,163 --> 01:17:17,300 ENRICHED TO GENERATE A MAGIC 1557 01:17:17,300 --> 01:17:19,636 SCORE WITH GENES HIGHLY 1558 01:17:19,636 --> 01:17:19,903 ENRICHED. 1559 01:17:19,903 --> 01:17:21,004 AND THE SCREEN CAN BE PERFORMED 1560 01:17:21,004 --> 01:17:22,772 IN THE ABSENCE OR PRESENCE OF 1561 01:17:22,772 --> 01:17:26,009 LRAs. 1562 01:17:26,009 --> 01:17:28,345 AND TO SHOW THE RESULTS IN THE 1563 01:17:28,345 --> 01:17:30,647 TIME POINT ON THE Y AXIS WE 1564 01:17:30,647 --> 01:17:33,116 PERFORMED THE SCREEN WITH AZD 1565 01:17:33,116 --> 01:17:35,719 AND ON THE X AXIS PERFORMED WITH 1566 01:17:35,719 --> 01:17:37,687 DMSO AND THE UNTREATED CONDITION 1567 01:17:37,687 --> 01:17:39,456 AND I REVEALED THE GENE HITS IF 1568 01:17:39,456 --> 01:17:40,790 WE FOCUS ON THE OPEN CIRCLES AT 1569 01:17:40,790 --> 01:17:43,226 THE BOTTOM YOU CAN SEE WHEN WE 1570 01:17:43,226 --> 01:17:45,528 KNOCKOUT THE NON TARGETING 1571 01:17:45,528 --> 01:17:47,063 CONTROLS WE SEE LITTLE 1572 01:17:47,063 --> 01:17:47,864 ENRICHMENT. 1573 01:17:47,864 --> 01:17:50,033 HOWEVER, EVERY GENE HIT ABOVE 1574 01:17:50,033 --> 01:17:51,301 THERE KNOCKOUT IS PREDICTED TO 1575 01:17:51,301 --> 01:17:52,969 REVERSE LATENCY. 1576 01:17:52,969 --> 01:17:55,372 SO SOME OF THOSE HITS REVERSE 1577 01:17:55,372 --> 01:17:58,842 LATENCY IN THE ABSENCE OF LRAs 1578 01:17:58,842 --> 01:18:00,577 AND SOME PREDICTED TO IMPROVE. 1579 01:18:00,577 --> 01:18:02,646 I WANT TO DRAW YOUR ATTENTION TO 1580 01:18:02,646 --> 01:18:04,648 THE PREDICTIVE TO IMPROVE THE 1581 01:18:04,648 --> 01:18:06,683 TREATMENT WHEN KNOCKED OUT. 1582 01:18:06,683 --> 01:18:09,786 AND ADDITIONALLY I WANTED TO 1583 01:18:09,786 --> 01:18:16,326 HIGHLIGHT ING3 WHICH IS A FACTOR 1584 01:18:16,326 --> 01:18:19,062 WHEN KNOCK DOWN HAS BEEN SHOWN 1585 01:18:19,062 --> 01:18:22,132 TO I AM IMPROVE. 1586 01:18:22,132 --> 01:18:23,833 SO WHAT IS -- IMPROVE THIS. 1587 01:18:23,833 --> 01:18:26,202 AND THE INTEGRATOR IS A GENOME 1588 01:18:26,202 --> 01:18:29,539 WIDE ATTENUATOR OF 1589 01:18:29,539 --> 01:18:30,140 NON-PRODUCTIVE TRANSCRIPTION. 1590 01:18:30,140 --> 01:18:34,377 THE COMPLEX CAN DETECT ABERR 1591 01:18:34,377 --> 01:18:35,345 ABERRANCES FROM THE 1592 01:18:35,345 --> 01:18:39,582 TRANSCRIPTION TO ELONGATION AND 1593 01:18:39,582 --> 01:18:43,086 IT HAS TWO MODULES. 1594 01:18:43,086 --> 01:18:47,724 A PHOSPHOTASE AND A CLEAVAGE 1595 01:18:47,724 --> 01:18:52,562 MODULE WITH WHICH TO CLEAVE AND 1596 01:18:52,562 --> 01:18:54,331 TERMINATE TRANSCRIPTION AND THE 1597 01:18:54,331 --> 01:18:55,598 ELONGATION STEP IS WHERE IT WAS 1598 01:18:55,598 --> 01:18:58,335 SEEN IN THE PRIMARY CELL SYSTEM. 1599 01:18:58,335 --> 01:19:01,204 SO OUR HYPOTHESIS THE INTEGRATOR 1600 01:19:01,204 --> 01:19:02,272 COMPLEX IS BLOCKING HIV 1601 01:19:02,272 --> 01:19:03,840 TRANSCRIPTION AT THE ELONGATION 1602 01:19:03,840 --> 01:19:09,112 LEVEL AND THEREFORE KNOCKING OUT 1603 01:19:09,112 --> 01:19:10,380 INTS12 SHOULD INCREASE 1604 01:19:10,380 --> 01:19:10,714 TRANSCRIPTION. 1605 01:19:10,714 --> 01:19:13,183 ONE ASSAY WE USED TO VALIDATE 1606 01:19:13,183 --> 01:19:15,118 THIS IS TOTAL RNA SEQ AND TOOK 1607 01:19:15,118 --> 01:19:16,987 THE CELLS TREATED AND/OR KNOCKED 1608 01:19:16,987 --> 01:19:24,594 OUT OF CRISPR AND WE DID THIS IN 1609 01:19:24,594 --> 01:19:31,568 BIOLOGICAL TRIPLICATE AND 1610 01:19:31,568 --> 01:19:34,304 MEASURES HOW UP OR DOWN 1611 01:19:34,304 --> 01:19:36,539 REGULATED VARIOUS GENES ARE AND 1612 01:19:36,539 --> 01:19:38,775 MEASURED HOW EXPRESSED THE GENES 1613 01:19:38,775 --> 01:19:38,942 ARE. 1614 01:19:38,942 --> 01:19:40,944 HIGHLY EXPRESSED ON THE RIGHT. 1615 01:19:40,944 --> 01:19:43,113 AND WE CAN SEE THAT FROM AZD 1616 01:19:43,113 --> 01:19:45,482 TREATMENT ALONE WE SEE THE 1617 01:19:45,482 --> 01:19:48,718 ROBUST INDUCTION OF HIV SO 1618 01:19:48,718 --> 01:19:50,387 THERE'S A LOG TWOFOLD CHANGE AND 1619 01:19:50,387 --> 01:19:53,590 HIGHLY EXPRESSED. 1620 01:19:53,590 --> 01:19:55,625 AND OF THE HOST GENES AFFECTED 1621 01:19:55,625 --> 01:19:59,496 THERE'S 80 UPREGULATED AND 306 1622 01:19:59,496 --> 01:19:59,863 DOWN REGULATED. 1623 01:19:59,863 --> 01:20:02,766 MOST OF THOSE UP OR DOWN 1624 01:20:02,766 --> 01:20:03,967 REGULATED ARE NOT HIGHLY 1625 01:20:03,967 --> 01:20:04,234 EXPRESSED. 1626 01:20:04,234 --> 01:20:06,836 SO HIV IS THE MOST EFFECTIVE 1627 01:20:06,836 --> 01:20:08,705 FROM THE TREATMENT AND SPECIFIC. 1628 01:20:08,705 --> 01:20:13,910 EXCITINGLY WHEN WE LOOKED AT OUR 1629 01:20:13,910 --> 01:20:17,313 INTS 12 KNOCKOUT WE SEE IT ALSO 1630 01:20:17,313 --> 01:20:20,450 INDUCES HIV TO SIMILAR LEVELS AT 1631 01:20:20,450 --> 01:20:26,423 A TWOFOLD CHANGE AND LESS 1632 01:20:26,423 --> 01:20:29,092 DYSREGULATION OF THE HOST AND 1633 01:20:29,092 --> 01:20:34,364 COULD BE A GOOD CANDIDATE FOR 1634 01:20:34,364 --> 01:20:35,965 LRAs. 1635 01:20:35,965 --> 01:20:38,368 WE SEE A FURTHER INDUCTION OF 1636 01:20:38,368 --> 01:20:41,938 HIV AND MORE DYSREGULATION OF 1637 01:20:41,938 --> 01:20:44,307 THE HOST BUT COMPARED TO A TOXIC 1638 01:20:44,307 --> 01:20:46,242 ACTIVATOR WE SEE THOUSANDS OF 1639 01:20:46,242 --> 01:20:47,043 HIGHLY EXPRESSED GENES 1640 01:20:47,043 --> 01:20:48,878 DYSREGULATED IN THAT CASE AND 1641 01:20:48,878 --> 01:20:50,213 HERE WE'RE ONLY SEEING ABOUT 1642 01:20:50,213 --> 01:20:50,480 200. 1643 01:20:50,480 --> 01:20:53,817 AND SO WE BELIEVE THAT WE NOT 1644 01:20:53,817 --> 01:20:55,485 ONLY SEE A POTENT INCREASE FROM 1645 01:20:55,485 --> 01:20:58,388 THE KNOCKOUT BUT OUR RESULTS ARE 1646 01:20:58,388 --> 01:20:59,923 FAIRLY SPECIFIC. 1647 01:20:59,923 --> 01:21:02,392 SO IN COLLABORATION WITH THE 1648 01:21:02,392 --> 01:21:05,161 BROWN LAB AND THIS SHOULD SAY 1649 01:21:05,161 --> 01:21:09,566 THE ARCHIN LAB WE BROUGHT IT 1650 01:21:09,566 --> 01:21:12,435 INTO AN EX VIVO SYSTEM AND TOOK 1651 01:21:12,435 --> 01:21:16,272 CELLS AND KNOCKED THEM OUT FOR 1652 01:21:16,272 --> 01:21:18,908 NON-TARGETING CONTROL AND 1653 01:21:18,908 --> 01:21:19,843 REACTIVATED THEM AND MEASURED 1654 01:21:19,843 --> 01:21:22,011 RNA IN THE SUPER LATENT. 1655 01:21:22,011 --> 01:21:23,379 WHEN I SHOW THE RESULTS FROM 1656 01:21:23,379 --> 01:21:29,953 THREE DONORS AND WE LOOK AT THE 1657 01:21:29,953 --> 01:21:33,256 NON-TARGETING CONTROL IN TWO OF 1658 01:21:33,256 --> 01:21:36,559 THE THREE WE SEE REACTIVATION 1659 01:21:36,559 --> 01:21:39,162 FROM KNOCKING IT OUT ON ITS OWN 1660 01:21:39,162 --> 01:21:40,930 WHICH IS EXCITING TO SEE AND THE 1661 01:21:40,930 --> 01:21:46,102 DONOR ON THE LEFT COMPARING OURA 1662 01:21:46,102 --> 01:21:50,373 ZZ AND KNOCKOUT WE SEE THE 1663 01:21:50,373 --> 01:21:53,409 ELONGATION KNOCK OUTWHERE THE 1664 01:21:53,409 --> 01:21:55,478 COMBINATION IS NOT WORKING WELL 1665 01:21:55,478 --> 01:21:58,148 AND WHEN PAIRED WE SEE ROBUST 1666 01:21:58,148 --> 01:22:00,049 ACTIVATION OF HIV. 1667 01:22:00,049 --> 01:22:02,385 AND LOOKING AT OTHER DONORS THE 1668 01:22:02,385 --> 01:22:04,721 ONE IN THE MIDDLE HAS A SMALLER 1669 01:22:04,721 --> 01:22:07,924 RESERVOIR SO THE VALUES ARE A 1670 01:22:07,924 --> 01:22:10,126 BIT MORE MESSY BUT SEE AN 1671 01:22:10,126 --> 01:22:10,827 INCREASE FROM THE KNOCKOUT. 1672 01:22:10,827 --> 01:22:13,596 THIS IS EXCITING BECAUSE IT 1673 01:22:13,596 --> 01:22:14,764 INDICATED OUR SCREENING WAS ABLE 1674 01:22:14,764 --> 01:22:18,301 TO PREDICT A BLOCK THAT EXISTS 1675 01:22:18,301 --> 01:22:19,936 IN PRIMARY CELLS. 1676 01:22:19,936 --> 01:22:23,706 SO TO SUMMARIZE I'VE SHOWN HIV 1677 01:22:23,706 --> 01:22:26,342 TRANSCRIPTION IS BLOCKED AT THE 1678 01:22:26,342 --> 01:22:27,310 HIV LEVEL. 1679 01:22:27,310 --> 01:22:29,946 IF YOU'D LIKE MORE MECHANISTIC 1680 01:22:29,946 --> 01:22:32,348 DETAILS WE'LL HAVE A DETAIL IN 1681 01:22:32,348 --> 01:22:35,351 BIO ARCHIVE AND THERE WILL BE 1682 01:22:35,351 --> 01:22:38,021 MORE WHEN IT'S PUBLISHED AND 1683 01:22:38,021 --> 01:22:40,890 THERE'S A VIABLE DRUG TARGET FOR 1684 01:22:40,890 --> 01:22:44,227 IMPROVING LRAs AND THE LABS ARE 1685 01:22:44,227 --> 01:22:49,933 DEVELOPING INHIBITORS TO ING3 1686 01:22:49,933 --> 01:23:00,443 AND INTS12 SHOULD BE EXPLORED 1687 01:23:02,011 --> 01:23:02,812 FURTHER AND ADDITIONALLY DRUGS 1688 01:23:02,812 --> 01:23:06,382 MAY BE IDENTIFIED TO TARGET 1689 01:23:06,382 --> 01:23:09,919 INTS12 TO IMPROVE LATENCY AND 1690 01:23:09,919 --> 01:23:20,463 WITH THAT THANK YOU AND I'LL LET 1691 01:23:22,966 --> 01:23:24,267 THE NEXT SPEAKER COME TO THE 1692 01:23:24,267 --> 01:23:32,942 PODIUM. 1693 01:23:32,942 --> 01:23:34,644 SO I HAVE MY LAB'S EFFORTS TO 1694 01:23:34,644 --> 01:23:36,546 TRY TO FIND NEW THINGS THAT 1695 01:23:36,546 --> 01:23:37,080 REGULATE HIV. 1696 01:23:37,080 --> 01:23:40,917 PARTICULARLY FOCUSSING ON TWO 1697 01:23:40,917 --> 01:23:50,393 THINGS THAT CHEMICAL JEANS AND 1698 01:23:50,393 --> 01:23:52,729 WE LOOK FOR GENES THAT REGULATE 1699 01:23:52,729 --> 01:23:54,097 LATENCY AND HAVE DONE SCREENS 1700 01:23:54,097 --> 01:23:56,566 WITH CHEMICALS AND WITH CRISPR 1701 01:23:56,566 --> 01:24:00,637 TO TRY TO FIND THESE THINGS AND 1702 01:24:00,637 --> 01:24:03,506 FOUND TWO THINGS. 1703 01:24:03,506 --> 01:24:07,844 WE THINK ETS 1 IS REPRESSING AND 1704 01:24:07,844 --> 01:24:16,252 WE THINK SEDT2 CAN REPRESS AND 1705 01:24:16,252 --> 01:24:23,192 WE HAVE A BROUGHT REACTIVATION 1706 01:24:23,192 --> 01:24:25,795 OF THE RESERVOIR AND WE DID AN 1707 01:24:25,795 --> 01:24:28,765 OMICS EXPERIMENT TAKE BEING HIV 1708 01:24:28,765 --> 01:24:34,671 INFECT WILL CD 8 T CELLS AROUND 1709 01:24:34,671 --> 01:24:36,739 COMBINED SINGLE CELL ATAC SEQ 1710 01:24:36,739 --> 01:24:38,875 AND YOU GET THE CHROMATIN 1711 01:24:38,875 --> 01:24:42,011 STRUCTURE AND WE CAN IDENTIFY 1712 01:24:42,011 --> 01:24:42,945 DIFFERENTLY EXPRESSED GENES 1713 01:24:42,945 --> 01:24:45,648 ACROSS THE POPULATION AND 1714 01:24:45,648 --> 01:24:50,553 DYNAMIC CHROMATIN PEAKS AND LOOK 1715 01:24:50,553 --> 01:24:52,522 AT THE BINDING SITES IN THE OPEN 1716 01:24:52,522 --> 01:24:59,028 CRHROMATIN AND WE CORRELATED WIH 1717 01:24:59,028 --> 01:24:59,962 THE EXPRESSION. 1718 01:24:59,962 --> 01:25:02,398 WHICH THINGS ARE CORRELATED WITH 1719 01:25:02,398 --> 01:25:03,666 HIV RNA LEVELS AND THEY'RE 1720 01:25:03,666 --> 01:25:08,004 LIKELY TO BE REGULATORS OF HIV. 1721 01:25:08,004 --> 01:25:09,706 SO THERE'S ABOUT 300 THINGS 1722 01:25:09,706 --> 01:25:10,340 CORRELATED WITH HIV. 1723 01:25:10,340 --> 01:25:14,177 AND THEN WE WORKED WITH THE 1724 01:25:14,177 --> 01:25:17,647 EMERMAN LAB AND DID A CRISPR 1725 01:25:17,647 --> 01:25:20,416 SCREEN KELLY DESCRIBED. 1726 01:25:20,416 --> 01:25:22,385 WE DID THE SCREEN IN 10.6 CELLS. 1727 01:25:22,385 --> 01:25:24,253 TO CUT A LONG STORY SHORT THESE 1728 01:25:24,253 --> 01:25:25,755 ARE THE HITS HERE. 1729 01:25:25,755 --> 01:25:27,090 AND I DON'T HAVE TIME TO GO 1730 01:25:27,090 --> 01:25:31,728 THROUGH ALL THE PIHITS. 1731 01:25:31,728 --> 01:25:33,730 THE THINGS ABOVE ARE WHEN YOU 1732 01:25:33,730 --> 01:25:35,398 KNOCK IT OUT YOU GET MORE HIV 1733 01:25:35,398 --> 01:25:37,967 BEING RELEASED. 1734 01:25:37,967 --> 01:25:41,371 SO ETS1 IS A TRANSCRIPTION 1735 01:25:41,371 --> 01:25:46,409 FACTOR HIGHLY EXPRESSED IN T 1736 01:25:46,409 --> 01:25:52,248 CELLS AND THERE'S A BUNCH OF 1737 01:25:52,248 --> 01:25:54,384 PAPERS INDICATING A POSITIVE 1738 01:25:54,384 --> 01:25:56,386 FACTOR FOR HIV EXPRESSION. 1739 01:25:56,386 --> 01:25:57,954 WE'RE SURPRISED TO SEE IT SHOW 1740 01:25:57,954 --> 01:25:59,989 UP AS A REPRESSIVE FACTOR. 1741 01:25:59,989 --> 01:26:03,626 BUT FOLLOWED UP ON THIS AND 1742 01:26:03,626 --> 01:26:04,594 PROBABLY THE MOST INTERESTING 1743 01:26:04,594 --> 01:26:06,596 EXPERIMENT WAS TO KNOCK IT OUT 1744 01:26:06,596 --> 01:26:11,667 IN CELLS WITH PEOPLE WITH HIV. 1745 01:26:11,667 --> 01:26:14,370 WE HAVE CD4 T CELLS FROM 1746 01:26:14,370 --> 01:26:24,647 DIFFERENT DONORS AND CITES 1747 01:26:24,647 --> 01:26:27,216 CRISPR KNOCKOUT AND WE GET A 1748 01:26:27,216 --> 01:26:30,386 BONA FIDE REPRESSOR IN PEOPLE 1749 01:26:30,386 --> 01:26:31,921 WITH HIV. 1750 01:26:31,921 --> 01:26:34,123 WE'RE STILL TRYING TO FOLLOW UP 1751 01:26:34,123 --> 01:26:37,226 ON THE MECHANISM. 1752 01:26:37,226 --> 01:26:42,098 I DO RNA SEQ AND WE PROFILED 1753 01:26:42,098 --> 01:26:43,699 CELLS AND PE LOOKED AT GENES 1754 01:26:43,699 --> 01:26:44,767 GOING UP AND DOWN. 1755 01:26:44,767 --> 01:26:46,636 I DON'T HAVE TIME TO GO THROUGH 1756 01:26:46,636 --> 01:26:50,006 ALL THE DETAILS BUT WE FOUND ONE 1757 01:26:50,006 --> 01:26:52,909 GENE THAT WENT UP AND IT'S A 1758 01:26:52,909 --> 01:26:54,911 LONG CODING RNA PREVIOUSLY 1759 01:26:54,911 --> 01:26:57,213 PUBLISHED AS A POSITIVE FACTOR 1760 01:26:57,213 --> 01:26:58,748 FOR HIV EXPRESSION AND 1761 01:26:58,748 --> 01:27:00,716 POSITIVELY REGULATED SO MAYBE 1762 01:27:00,716 --> 01:27:02,819 THIS IS HOW THE KNOCKOUT WORKS 1763 01:27:02,819 --> 01:27:05,521 YOU KNOCKOUT AND IT PROMOTES 1764 01:27:05,521 --> 01:27:05,855 HIV. 1765 01:27:05,855 --> 01:27:08,825 TO TEST THAT HYPOTHESIS WE DID A 1766 01:27:08,825 --> 01:27:10,226 DOUBLE KNOCKOUT IN A PRIMARY 1767 01:27:10,226 --> 01:27:14,063 MODEL MY LAB USES. 1768 01:27:14,063 --> 01:27:15,565 WE TAKE T CELLS AND EXPRESS THEM 1769 01:27:15,565 --> 01:27:18,267 WITH A CLONE OF HIV AND INFECT 1770 01:27:18,267 --> 01:27:21,370 THE CELLS IN THE LAB. 1771 01:27:21,370 --> 01:27:23,506 WHEN YOU KNOCKOUT YOU SEE RNA 1772 01:27:23,506 --> 01:27:29,479 LEVELS GO DOWN AND WHEN I DO A 1773 01:27:29,479 --> 01:27:32,181 DOUBLE KNOCKOUT TOGETHER IT 1774 01:27:32,181 --> 01:27:34,450 ABROGATES THE ABROGATES THE 1775 01:27:34,450 --> 01:27:38,387 KNOCKOUT AND PART OF THE EFFECT 1776 01:27:38,387 --> 01:27:40,156 IS THROUGH UP REGULATING. 1777 01:27:40,156 --> 01:27:44,961 THIS IS OUR MODEL. 1778 01:27:44,961 --> 01:27:46,629 WE THINK IT'S REPRESSING CELLS 1779 01:27:46,629 --> 01:27:57,173 AND IT POSITIVELY ACTIVATES HIV. 1780 01:28:00,142 --> 01:28:04,647 AND THIS IS A TRANSFERASE. 1781 01:28:04,647 --> 01:28:07,049 IT CREATES THE TRIMETHYL MARK 1782 01:28:07,049 --> 01:28:08,684 HERE AND THIS WAS INTERESTING. 1783 01:28:08,684 --> 01:28:11,787 THIS MARK IS ABUNDANTLY FOUND ON 1784 01:28:11,787 --> 01:28:16,392 THE ACTIVELY TRANSCRIBED GENES. 1785 01:28:16,392 --> 01:28:21,764 THE TRI METHYL IS A KEY 1786 01:28:21,764 --> 01:28:23,366 INDICATION FACTOR FOR HIV. 1787 01:28:23,366 --> 01:28:27,737 WHAT HAPPENS IF YOU REMOVE THE 1788 01:28:27,737 --> 01:28:28,504 TRI METHYL? 1789 01:28:28,504 --> 01:28:31,073 HOW DOES IT CHANGE THE WAY HIV 1790 01:28:31,073 --> 01:28:32,775 GETS EXPRESSED. 1791 01:28:32,775 --> 01:28:43,252 WE HAVE AN INHIBITOR AND WE 1792 01:28:49,859 --> 01:28:52,428 INFECT WITH HIV AND SEE NOTHING 1793 01:28:52,428 --> 01:28:53,529 LAND. 1794 01:28:53,529 --> 01:28:59,335 IT DOES NOT SEE THE TRIMETHYL 1795 01:28:59,335 --> 01:29:04,507 HAS ANOTHER WAY TO INFECT AND IT 1796 01:29:04,507 --> 01:29:06,275 DOESN'T DEPEND AND WE PRE 1797 01:29:06,275 --> 01:29:08,210 TREATED WITH THIS INHIBITER. 1798 01:29:08,210 --> 01:29:13,416 THE INTEGRATION SITES CHANGED. 1799 01:29:13,416 --> 01:29:22,425 HIV LIKES TO ACTIVATE WITH THE 1800 01:29:22,425 --> 01:29:23,859 ACTIVELY TRANSCRIBED GENES AND 1801 01:29:23,859 --> 01:29:27,830 WE HAVE CHROMATIN MODEL BASED ON 1802 01:29:27,830 --> 01:29:29,565 THE MARKS. 1803 01:29:29,565 --> 01:29:32,935 WHEN YOU HAVE THE DEPLETION YOU 1804 01:29:32,935 --> 01:29:35,237 SEE FEWER INTEGRATION IN THE 1805 01:29:35,237 --> 01:29:43,179 ACTIVELY TRANBY BY -- 1806 01:29:43,179 --> 01:29:45,314 TRANSCRIBED GENES AND THEY MOVE 1807 01:29:45,314 --> 01:29:46,482 HERE TO LIKE A DIFFERENT 1808 01:29:46,482 --> 01:29:46,849 NEIGHBORHOOD. 1809 01:29:46,849 --> 01:29:48,050 WE LOOKED AT LATENCY. 1810 01:29:48,050 --> 01:29:50,486 WE SOMEWHERE THE MODEL TO INFECT 1811 01:29:50,486 --> 01:29:52,822 CELLS AND ENRICH FOR ACTIVELY 1812 01:29:52,822 --> 01:29:54,023 INFECTED CELLS AND CULTURE THEM 1813 01:29:54,023 --> 01:29:55,691 FOR A PERIOD OF TIME. 1814 01:29:55,691 --> 01:29:57,226 YOU CAN SEE CELLS AT TRANSITION 1815 01:29:57,226 --> 01:29:58,260 REMAINING POSITIVE TO NEGATIVE 1816 01:29:58,260 --> 01:30:02,698 AND COUNT THE YELLS BEING -- 1817 01:30:02,698 --> 01:30:04,233 CELLS AND MEASURE AND IN THE 1818 01:30:04,233 --> 01:30:06,369 PRESENCE OF THE INHIBITOR WE SEE 1819 01:30:06,369 --> 01:30:12,008 MORE LATENTLY INFECTED CELLS AND 1820 01:30:12,008 --> 01:30:13,643 CELLS SHUT DOWN AND THE ACTIVITY 1821 01:30:13,643 --> 01:30:17,580 IS REQUIRED TO KEEP HIV ON AN 1822 01:30:17,580 --> 01:30:18,948 ACTIVELY TRANSCRIBED STATE. 1823 01:30:18,948 --> 01:30:20,950 I THINK IT'S DIFFERENT FROM THE 1824 01:30:20,950 --> 01:30:22,318 INTEGRATION SITE PHENOMENON. 1825 01:30:22,318 --> 01:30:23,886 I DON'T HAVE TIME TO GO TO THE 1826 01:30:23,886 --> 01:30:34,130 DETAILS LATER. 1827 01:30:36,165 --> 01:30:38,401 WE LOOKED AT TOTAL RNA LEVELS 1828 01:30:38,401 --> 01:30:42,004 AND WE SAW IT CHANGES LYSINE. 1829 01:30:42,004 --> 01:30:46,976 WE SEE MORE UNSPLICED VIRAL RNA. 1830 01:30:46,976 --> 01:30:53,082 SOMEHOW THE HISTONE AFFECT THE 1831 01:30:53,082 --> 01:30:54,517 EXPRESSION OF HIV. 1832 01:30:54,517 --> 01:30:57,286 THAT'S OUR BEST GUESS FOR HOW 1833 01:30:57,286 --> 01:30:58,387 THIS WORKS. 1834 01:30:58,387 --> 01:31:00,723 ANOTHER THING THAT WAS 1835 01:31:00,723 --> 01:31:03,125 POTENTIALLY USEFUL TAKING LATE 1836 01:31:03,125 --> 01:31:05,661 ENLY INFECTED CELLS YOU GET MORE 1837 01:31:05,661 --> 01:31:08,698 BANG FOR YOUR BUCK FROM CERTAIN 1838 01:31:08,698 --> 01:31:12,968 LRAs AND HYPERSENSITIZE THE 1839 01:31:12,968 --> 01:31:13,402 INHIBITORS. 1840 01:31:13,402 --> 01:31:18,474 YOU CAN KNOCK DOWN HIV 1841 01:31:18,474 --> 01:31:28,984 EXPRESSION AND HERE YOU GET A 1842 01:31:56,479 --> 01:31:59,115 BROADER EXPRESSION AND I'LL PASS 1843 01:31:59,115 --> 01:32:09,525 IT OFF NEXT TO HONGBING. 1844 01:32:21,804 --> 01:32:24,106 >> AND IT'S GREAT TO COME HERE 1845 01:32:24,106 --> 01:32:32,648 TO SHARE AN PRESENT OUR WORK. 1846 01:32:32,648 --> 01:32:34,383 AND IT IS POSSIBLE FOR 1847 01:32:34,383 --> 01:32:37,620 IMMUNOTHERAPY FOR HIV 1848 01:32:37,620 --> 01:32:37,987 ERADICATION. 1849 01:32:37,987 --> 01:32:41,557 SO KILLER T CELLS PLAY A ROLE IN 1850 01:32:41,557 --> 01:32:45,161 CONTROLLING HIV REPLICATION. 1851 01:32:45,161 --> 01:32:47,263 AND THE KILLER CELLS RECOGNIZE 1852 01:32:47,263 --> 01:32:48,631 INFECTED CELLS THROUGH A SMALL 1853 01:32:48,631 --> 01:32:52,368 PIECE OF HIV PRESENTED BY A 1854 01:32:52,368 --> 01:32:56,839 MOLECULE CALLED HLA-A-B OR C. 1855 01:32:56,839 --> 01:33:02,144 BECAUSE OF THE GLOBAL DIVERSITY 1856 01:33:02,144 --> 01:33:07,883 OF THE MOLECULE AND COVER THE 1857 01:33:07,883 --> 01:33:08,884 WHOLE POPULATION. 1858 01:33:08,884 --> 01:33:11,554 THE T CELLS CAN ALSO RECOGNIZE 1859 01:33:11,554 --> 01:33:14,456 HIV THROUGH ANOTHER MOLECULE 1860 01:33:14,456 --> 01:33:18,460 CALLED E. 1861 01:33:18,460 --> 01:33:29,004 AND THIS IS A NON-POLYMORPHISM. 1862 01:33:53,295 --> 01:33:59,401 AND THE T CELLS CAN AFFECT THE 1863 01:33:59,401 --> 01:34:02,404 IMMUNE CELLS AND THERE'S 1864 01:34:02,404 --> 01:34:07,343 POTENTIAL THROUGH THE T CELLS. 1865 01:34:07,343 --> 01:34:10,246 THERE'S A GREAT ADVANTAGE OF 1866 01:34:10,246 --> 01:34:12,081 IMMUNOTHERAPY AND IT'S 1867 01:34:12,081 --> 01:34:14,049 POLYMORPHIC SO THERE'S A 1868 01:34:14,049 --> 01:34:16,252 POSSIBILITY OF UNIVERSAL 1869 01:34:16,252 --> 01:34:17,586 IMMUNOTHERAPY AND HIV INFECTION. 1870 01:34:17,586 --> 01:34:23,058 E IS NOT DOWN REGULATED. 1871 01:34:23,058 --> 01:34:33,602 HOWEVER, THE HLA-A, B OR C ARE 1872 01:34:34,270 --> 01:34:36,939 DOWN REGULATED. 1873 01:34:36,939 --> 01:34:47,449 WE RECOGNIZED PEPTIDE AND ONE 1874 01:34:49,285 --> 01:34:52,621 CLONED T CELLS FOR ALL THREE 1875 01:34:52,621 --> 01:34:52,855 ACTORS. 1876 01:34:52,855 --> 01:34:57,993 SO HERE I JUST SHOW AN EXAMPLE 1877 01:34:57,993 --> 01:35:00,863 OF IL-9 CLONE AND AFTER PRIMING 1878 01:35:00,863 --> 01:35:05,901 WE CAN DETECT POSITIVE RESULTS 1879 01:35:05,901 --> 01:35:14,543 AND THE CLONE WITH THIS AND IT'S 1880 01:35:14,543 --> 01:35:16,912 LOW COMPARED TO T CELLS BECAUSE 1881 01:35:16,912 --> 01:35:20,416 THE BINDING AFFINITY OF TO THE 1882 01:35:20,416 --> 01:35:22,918 PEPTIDE IS MUCH LOWER THAN 1883 01:35:22,918 --> 01:35:31,860 CLASSIC T CELL. 1884 01:35:31,860 --> 01:35:35,564 AND AT DUKE THEY GENERATED 1885 01:35:35,564 --> 01:35:39,835 POTENT ANTIBODY. 1886 01:35:39,835 --> 01:35:50,412 SO VO 9 IS A SELF-HOST PEPTIDE 1887 01:35:50,412 --> 01:35:56,719 ORIGINATING FROM THE OTHER 1888 01:35:56,719 --> 01:36:06,028 MOLECULES. 1889 01:36:06,028 --> 01:36:08,964 AND WE USED THE VIRAL EXPRESSION 1890 01:36:08,964 --> 01:36:09,231 ASSAY. 1891 01:36:09,231 --> 01:36:10,933 BRIEFLY THE CD4 T CELLS FROM 1892 01:36:10,933 --> 01:36:12,701 HEALTHY DONOR WERE INFECTED WITH 1893 01:36:12,701 --> 01:36:22,745 HIV VIRUS AND CLONED FOR FIVE 1894 01:36:22,745 --> 01:36:25,948 DAYS AND QUANTIFIED THE INFECTED 1895 01:36:25,948 --> 01:36:27,683 CELLS AND I GIVE YOU TWO 1896 01:36:27,683 --> 01:36:28,117 EXAMPLES HERE. 1897 01:36:28,117 --> 01:36:33,956 THE MIDDLE ONE IS ONE OF OUR 1898 01:36:33,956 --> 01:36:39,895 IL-9 CLONE COMPARED TO THE 1899 01:36:39,895 --> 01:36:42,164 INFECTED CELLS ALONE WITHOUT T 1900 01:36:42,164 --> 01:36:45,667 CELL CLONE WE SEE REDUCTION OF 1901 01:36:45,667 --> 01:36:49,671 P24 POSITIVE CELLS IS OVER 87% 1902 01:36:49,671 --> 01:36:53,108 OF KILLING AND THE SECOND 1903 01:36:53,108 --> 01:36:54,543 EXAMPLE IS IL-9 CLONE. 1904 01:36:54,543 --> 01:37:00,082 AND THIS ONE SHOWED EVEN MORE 1905 01:37:00,082 --> 01:37:02,151 POTENT KILLING ACTIVITY. 1906 01:37:02,151 --> 01:37:12,628 IT'S NEARLY 97% INHIBITION. 1907 01:37:14,096 --> 01:37:18,033 AND WE THEN PERFORMED EXPRESSION 1908 01:37:18,033 --> 01:37:18,767 ASSAY. 1909 01:37:18,767 --> 01:37:24,173 THE GRAPH SHOWED THE EXAMPLE OF 1910 01:37:24,173 --> 01:37:27,109 TWO IL-9 ACTORS IN THE YELLOW 1911 01:37:27,109 --> 01:37:31,547 BARS. 1912 01:37:31,547 --> 01:37:37,953 AND IN THIS ASSAY WE AND THIS IS 1913 01:37:37,953 --> 01:37:41,190 A WELL STUDIED AND POTENT 1914 01:37:41,190 --> 01:37:42,524 FUNCTION. 1915 01:37:42,524 --> 01:37:50,499 SO YOU CAN SEE THE TRANSDUCTANTS 1916 01:37:50,499 --> 01:37:53,168 SHOWED POTENT INHIBITION ALMOST 1917 01:37:53,168 --> 01:37:55,337 CLEARING THE INFECTED T CELLS 1918 01:37:55,337 --> 01:38:02,111 BUT WORKED BEAUTIFULLY ON THE 1919 01:38:02,111 --> 01:38:03,412 DONORS ON THE POSITIVE AND WITH 1920 01:38:03,412 --> 01:38:07,683 THE ACCIST -- ACTIVE DONORS 1921 01:38:07,683 --> 01:38:11,753 THERE'S NO EFFECT BUT FOR THE 1922 01:38:11,753 --> 01:38:14,389 TCR WORKED FOR ALL DONORS. 1923 01:38:14,389 --> 01:38:18,360 THAT'S AN EXAMPLE OF THE 1924 01:38:18,360 --> 01:38:22,798 NON-POLYMORPHISM OF THE TCR. 1925 01:38:22,798 --> 01:38:28,770 NOW I'M TALKING ABOUT THE 1926 01:38:28,770 --> 01:38:29,505 FUNCTION. 1927 01:38:29,505 --> 01:38:35,310 WE TESTED THE ANTIBODY AND SO 1928 01:38:35,310 --> 01:38:36,712 ACTUALLY WE PRESENTED THIS 1929 01:38:36,712 --> 01:38:42,050 PEPTIDE TO THE MOLECULE 1930 01:38:42,050 --> 01:38:45,120 EXPRESSED MAINLY ON NK CELLS OR 1931 01:38:45,120 --> 01:38:49,591 SOME SUBSET OF CD 8 T CELLS. 1932 01:38:49,591 --> 01:38:56,165 SO TO INITIATE INHIBIT THE 1933 01:38:56,165 --> 01:39:03,539 SIGNAL TO BLOCK THE KILLING THE 1934 01:39:03,539 --> 01:39:04,907 ANTIBODY CAN BLOCK THE 1935 01:39:04,907 --> 01:39:05,641 INHIBITORY SIGNAL. 1936 01:39:05,641 --> 01:39:09,611 IF THEY CAN RESTORE THE KILLING 1937 01:39:09,611 --> 01:39:14,082 FUNCTION SO WHAT WE USED IS ONE 1938 01:39:14,082 --> 01:39:16,652 OF OUR CLONE SO IT SHOWED IN THE 1939 01:39:16,652 --> 01:39:17,953 BLUE BAR. 1940 01:39:17,953 --> 01:39:24,059 THIS CLONE HAS SHOWN MODEST 1941 01:39:24,059 --> 01:39:28,230 INHIBITION AND WE ADD THE 1942 01:39:28,230 --> 01:39:31,633 ANTIBODY AND YOU CAN SEE 1943 01:39:31,633 --> 01:39:32,901 SIGNIFICANT INCREASE ON THE 1944 01:39:32,901 --> 01:39:36,038 KILLING ACTIVITY WHICH SHOWED IN 1945 01:39:36,038 --> 01:39:39,675 THE PINK BOX. 1946 01:39:39,675 --> 01:39:42,244 SO SUMMARIZE WHAT WE HAVE DONE 1947 01:39:42,244 --> 01:39:44,746 SO FAR WE HAVE DEMONSTRATED FOR 1948 01:39:44,746 --> 01:39:48,750 THE FIRST TIME THAT THE E 1949 01:39:48,750 --> 01:39:53,188 RESTRICTED HIV CELLS CAN BE 1950 01:39:53,188 --> 01:39:55,224 PRIMED IN VITRO AND RECOGNIZE 1951 01:39:55,224 --> 01:39:58,393 NATURALLY PRESENTED HIV ACTORS 1952 01:39:58,393 --> 01:39:59,795 AND INFECTED CELLS. 1953 01:39:59,795 --> 01:40:03,799 AND IT IS VERY ENCOURAGING THAT 1954 01:40:03,799 --> 01:40:08,804 THE TCR INTO THE CD 8 T CELLS 1955 01:40:08,804 --> 01:40:11,940 WERE EFFECTIVE IN REDUCING VIRUS 1956 01:40:11,940 --> 01:40:14,409 REPLICATION AND TOGETHER WITH 1957 01:40:14,409 --> 01:40:18,814 THE ENHANCEMENT OF KILLING OF 1958 01:40:18,814 --> 01:40:23,719 THE ANTIBODY COULD OFFER A NOVEL 1959 01:40:23,719 --> 01:40:26,388 THERAPEUTIC APPROACH TO HIV 1960 01:40:26,388 --> 01:40:28,557 ERADICATION. 1961 01:40:28,557 --> 01:40:31,193 OUR HYPOTHESIS IS THE 1962 01:40:31,193 --> 01:40:34,396 E-RESTRICTED LOW AFFINITY T 1963 01:40:34,396 --> 01:40:37,199 CELLS MAY BE LESS SUSCEPTIBLE TO 1964 01:40:37,199 --> 01:40:41,270 CELL DEATHS IN VIVO AND COULD BE 1965 01:40:41,270 --> 01:40:43,672 VERY IMPORTANT IN THERAPY 1966 01:40:43,672 --> 01:40:46,742 PERSISTENCE IN HIV ERADICATION. 1967 01:40:46,742 --> 01:40:50,045 AND SO FINALLY I WOULD LIKE TO 1968 01:40:50,045 --> 01:40:53,515 THANK ALL MY COLLEAGUES AT 1969 01:40:53,515 --> 01:40:55,851 OXFORD AND OUR COLLABORATORS AT 1970 01:40:55,851 --> 01:40:58,987 UNC, DUKE AND UAB FOR THE GREAT 1971 01:40:58,987 --> 01:41:00,055 COLLABORATION WORK. 1972 01:41:00,055 --> 01:41:10,232 THANK YOU. 1973 01:41:36,124 --> 01:41:40,362 >> IT'S GOOD TO BE HIRE. 1974 01:41:40,362 --> 01:41:41,063 THE -- HERE. 1975 01:41:41,063 --> 01:41:42,531 THE COLLABORATORY HAS BEEN 1976 01:41:42,531 --> 01:41:43,932 EXCITING AND TRIED TO GIVE A 1977 01:41:43,932 --> 01:41:51,473 GENERAL SENSE OF WHERE WE ARE. 1978 01:41:51,473 --> 01:41:52,541 I'VE BEEN ONLY BEEN INVOLVED IN 1979 01:41:52,541 --> 01:41:54,643 THE LAST TWO ITERATIONS. 1980 01:41:54,643 --> 01:41:56,278 THE WORK THAT WE'LL BE 1981 01:41:56,278 --> 01:41:58,013 DISCUSSING AND THIS IS THE PLAIN 1982 01:41:58,013 --> 01:42:00,415 LANGUAGE SUMMARY THE IMPORTANCE 1983 01:42:00,415 --> 01:42:02,451 OF USING THE NONHUMAN PRIMATE 1984 01:42:02,451 --> 01:42:04,486 MODEL AND USING THE PARTICULAR 1985 01:42:04,486 --> 01:42:06,121 LATENCY REVERSAL AGENT ALONE OR 1986 01:42:06,121 --> 01:42:11,526 IN COMBINATION WITH OTHER AGENT 1987 01:42:11,526 --> 01:42:21,970 THAT PROMOTE AND THE KEY 1988 01:42:40,589 --> 01:42:43,258 COMPONENT OF THE SHOCK AND KILL 1989 01:42:43,258 --> 01:42:50,399 APPROACH IS THE LATENCY AGENT I 1990 01:42:50,399 --> 01:42:51,233 MENTIONED THE CONVERSATION 10 1991 01:42:51,233 --> 01:42:52,634 YEARS AGO. 1992 01:42:52,634 --> 01:42:54,436 THIS ONE WAS A CONVERSATION I 1993 01:42:54,436 --> 01:43:00,075 THINK WAS EIGHT OR NINE YEARS 1994 01:43:00,075 --> 01:43:04,413 AGO AND WE UNDER IN THE BLUE 1995 01:43:04,413 --> 01:43:06,381 JACKET AND I WAS CALLED UP AND 1996 01:43:06,381 --> 01:43:08,216 GOT THE AMAZING COMPOUND THAT 1997 01:43:08,216 --> 01:43:11,720 REVERSES LATENCY TO A LEVEL I'VE 1998 01:43:11,720 --> 01:43:14,122 NEVER SEEN BEFORE. 1999 01:43:14,122 --> 01:43:16,091 AND WE DECIDED AND STARTED 2000 01:43:16,091 --> 01:43:26,501 PUTTING IT INTO MONKEYS AND THE 2001 01:43:26,501 --> 01:43:29,905 IDEA IS THAT A STRONG CELL 2002 01:43:29,905 --> 01:43:31,840 SPECIFIC IMMUNE CELL SPECIFIC 2003 01:43:31,840 --> 01:43:36,077 LATENCY REVERSING CAN BE 2004 01:43:36,077 --> 01:43:43,618 OBTAINED BY USING THE CONCEPT OF 2005 01:43:43,618 --> 01:43:44,119 MEMETICS. 2006 01:43:44,119 --> 01:43:46,121 THOSE ARE ACTIVATOR OF THE 2007 01:43:46,121 --> 01:43:50,392 PATHWAYS AND INHIBITORS OF 2008 01:43:50,392 --> 01:43:56,198 APOPTOSIS AND SHOWED LATENCY 2009 01:43:56,198 --> 01:44:03,972 REVERSE ACTIVITY AND OUR WORK IN 2010 01:44:03,972 --> 01:44:05,807 MONKEYS THEY WERE VERY EFFECTIVE 2011 01:44:05,807 --> 01:44:07,609 AT REVERSING LATENCY BUT WE'LL 2012 01:44:07,609 --> 01:44:08,577 COME BACK TO THAT. 2013 01:44:08,577 --> 01:44:12,280 THIS IS SOMETHING I ALLUDED TO 2014 01:44:12,280 --> 01:44:12,514 BEFORE. 2015 01:44:12,514 --> 01:44:21,323 MONKEY STUDIES IN WHICH WE ADD 2016 01:44:21,323 --> 01:44:23,658 SOMETHING TO THE ANTIVIRAL 2017 01:44:23,658 --> 01:44:24,693 THERAPY TO DISRUPT THE RESERVOIR 2018 01:44:24,693 --> 01:44:27,395 ARE IN STUDIES WHERE WE IMPACT 2019 01:44:27,395 --> 01:44:28,697 THE ESTABLISHMENT OF THE 2020 01:44:28,697 --> 01:44:30,732 RESERVOIR AND GIVEN AT THE TIME 2021 01:44:30,732 --> 01:44:32,400 OF THE STUDIES THAT IMPACT ON 2022 01:44:32,400 --> 01:44:35,504 THE PERSISTENCE OF THE RESERVOIR 2023 01:44:35,504 --> 01:44:37,038 AND GIVE SO-CALLED PURE 2024 01:44:37,038 --> 01:44:42,444 INTERVENTION AFTER A PROLONGED 2025 01:44:42,444 --> 01:44:45,714 PERIOD OF ART. 2026 01:44:45,714 --> 01:44:49,718 I'LL FOCUS FIRST ON A STUDY THIS 2027 01:44:49,718 --> 01:44:51,586 WAS LED BY VICTOR WITH THE 2028 01:44:51,586 --> 01:44:55,557 POSTDOC CHRIS NIXON AT THE TIME. 2029 01:44:55,557 --> 01:44:58,994 AND THE STUDY WAS 2030 01:44:58,994 --> 01:44:59,561 STRAIGHTFORWARD. 2031 01:44:59,561 --> 01:45:04,733 IT WAS AN ABSOLUTE RESULT IN 2032 01:45:04,733 --> 01:45:08,370 HUMANIZED MICE AND INFECTED 2033 01:45:08,370 --> 01:45:10,739 MACAQUES AND GIVE MULTIPLE DOSES 2034 01:45:10,739 --> 01:45:17,178 AND GET A ROBUST REVERSAL OF 2035 01:45:17,178 --> 01:45:18,079 LATENCY. 2036 01:45:18,079 --> 01:45:23,218 THIS REVERSAL HAS NO IMPACT ON 2037 01:45:23,218 --> 01:45:27,756 THE SIZE OF THE RESERVOIR AND 2038 01:45:27,756 --> 01:45:29,324 THEY WENT BACK TO LATENCY AND 2039 01:45:29,324 --> 01:45:31,626 THE NUMBER DIDN'T CHANGE OVER 2040 01:45:31,626 --> 01:45:31,826 TIME. 2041 01:45:31,826 --> 01:45:34,195 ONE THING WE DID IN OUR GROUP IS 2042 01:45:34,195 --> 01:45:37,032 TO DEMONSTRATE THIS TREATMENT 2043 01:45:37,032 --> 01:45:39,634 WAS ACTUALLY SYNERGISTIC WITH CD 2044 01:45:39,634 --> 01:45:41,903 8 DEPLETION. 2045 01:45:41,903 --> 01:45:46,174 WHEN YOU PULL OUT THE CLOGGING 2046 01:45:46,174 --> 01:45:49,778 OF LATENCY OF VIRAL EXPRESSION 2047 01:45:49,778 --> 01:45:52,647 AND DONE BY THE CD 8 YOU HAVE 2048 01:45:52,647 --> 01:45:57,285 LYMPH NODE THE ACTIVITY OF THE 2049 01:45:57,285 --> 01:45:59,054 LATENCY REVERSING AGENT TO BE 2050 01:45:59,054 --> 01:46:02,223 BECOME MORE POWERFUL AND SAME WE 2051 01:46:02,223 --> 01:46:04,759 SAW IN THE STUDY A FEW YEARS 2052 01:46:04,759 --> 01:46:04,926 AGO. 2053 01:46:04,926 --> 01:46:07,329 AND THAT'S PART OF THE WORK I 2054 01:46:07,329 --> 01:46:11,499 WAS REFERRING THAT JUSTIFIED THE 2055 01:46:11,499 --> 01:46:16,471 REASON WHY THIS IS A PRO LATENCY 2056 01:46:16,471 --> 01:46:18,239 ACTIVITY OF THE CD 8 T CELLS. 2057 01:46:18,239 --> 01:46:25,413 THE NEXT STUDY WAS LED WITH MOD 2058 01:46:25,413 --> 01:46:27,549 AND OTHERS AND THIS WAS TRYING 2059 01:46:27,549 --> 01:46:31,219 TO SEE IF THE REVERSAL OF 2060 01:46:31,219 --> 01:46:40,028 LATENCY INDUCED BY AZD5582 COULD 2061 01:46:40,028 --> 01:46:46,568 BE HELPED BY ADMINISTERING 2062 01:46:46,568 --> 01:46:48,203 MONOCLONAL ANTIBODIES TO REDUCE 2063 01:46:48,203 --> 01:46:50,405 THE RESERVOIR SIZE. 2064 01:46:50,405 --> 01:46:52,574 THIS STUDY WAS I GUESS THE 2065 01:46:52,574 --> 01:46:55,443 CLASSICAL STUDY YOU CAN SEE AS 2066 01:46:55,443 --> 01:46:57,078 THE GLASS HALF FULL OR HALF 2067 01:46:57,078 --> 01:46:57,679 EMPTY. 2068 01:46:57,679 --> 01:47:00,048 BUT THE REALITY IS THAT WE SAW 2069 01:47:00,048 --> 01:47:05,253 FOR THE FIRST TIME A SIGNAL OF 2070 01:47:05,253 --> 01:47:07,055 AZD5582 IN REDUCING THE 2071 01:47:07,055 --> 01:47:08,456 RESERVOIR SIDES WHEN USED 2072 01:47:08,456 --> 01:47:11,192 TOGETHER WITH THOSE NEUTRALIZING 2073 01:47:11,192 --> 01:47:11,459 ANTIBODY. 2074 01:47:11,459 --> 01:47:14,295 THIS WORK WAS PUBLISHED A WHILE 2075 01:47:14,295 --> 01:47:20,435 AGO AND AGAIN OPENED UP THE IDEA 2076 01:47:20,435 --> 01:47:23,938 THAT AZD5582 NOT WITHSTANDING 2077 01:47:23,938 --> 01:47:25,407 THE COMPLICATION IN PEOPLE WE 2078 01:47:25,407 --> 01:47:29,544 ALL RECOGNIZE BUT AS A PROOF OF 2079 01:47:29,544 --> 01:47:34,883 PRINCIPLE OF A MOLECULAR 2080 01:47:34,883 --> 01:47:37,619 MECHANISM MAY END UP 2081 01:47:37,619 --> 01:47:38,520 METABOLIZING THE PERSISTENT 2082 01:47:38,520 --> 01:47:38,987 RESERVOIR. 2083 01:47:38,987 --> 01:47:42,424 THE NEXT STUDY WAS SEEING 2084 01:47:42,424 --> 01:47:47,529 SYNERGY BETWEEN AZD5582 AND 2085 01:47:47,529 --> 01:47:51,666 REVERSAL EFFECT BY THE SUPER 2086 01:47:51,666 --> 01:47:51,900 AGONIST. 2087 01:47:51,900 --> 01:47:54,169 BECAUSE OF THE PROBLEMS WE HAD 2088 01:47:54,169 --> 01:47:57,906 TO REDIRECT OUR EFFORTS BY USING 2089 01:47:57,906 --> 01:48:02,410 ANOTHER IL-15 SUPER AGONIST THAT 2090 01:48:02,410 --> 01:48:05,413 WAS GENERATED AND DEVELOPED IN A 2091 01:48:05,413 --> 01:48:07,682 SERIES OF STUDIES AND AGAIN WE 2092 01:48:07,682 --> 01:48:08,616 CAN TALK DURING THE DISCUSSION 2093 01:48:08,616 --> 01:48:10,852 WHAT IS SIMILAR OR DIFFERENT 2094 01:48:10,852 --> 01:48:12,187 BETWEEN THE MOLECULE BUT IT'S 2095 01:48:12,187 --> 01:48:15,590 THE BEST WE GET IN TERMS OF 2096 01:48:15,590 --> 01:48:17,492 REPLICATING THE EFFECT. 2097 01:48:17,492 --> 01:48:24,566 THE STUDY NOW IS A STUDY OF 2098 01:48:24,566 --> 01:48:26,768 AZD5582 WITHOUT THE SUPER 2099 01:48:26,768 --> 01:48:29,637 AGONIST AND TO SEE THE IMPACT ON 2100 01:48:29,637 --> 01:48:35,276 THE ESTABLISHMENT OF THE 2101 01:48:35,276 --> 01:48:36,811 RESERVOIR STUDY WAS LED IN THE 2102 01:48:36,811 --> 01:48:37,779 FIRST ROUND. 2103 01:48:37,779 --> 01:48:41,583 AND THIS IS WHAT SHARON LEWIN 2104 01:48:41,583 --> 01:48:42,117 WAS ALLUDING TO. 2105 01:48:42,117 --> 01:48:43,885 THESE ARE STUDIES WHERE THE 2106 01:48:43,885 --> 01:48:45,353 READOUTS ARE THE SLOPE OF 2107 01:48:45,353 --> 01:48:48,123 DECLINE OF VIREMIA. 2108 01:48:48,123 --> 01:48:50,225 THE CLASSICAL MODEL SAID IF 2109 01:48:50,225 --> 01:48:54,829 CELLS DIE FASTER THE VIREMIA 2110 01:48:54,829 --> 01:48:58,399 WILL BECOME MORE STEEP AND IN 2111 01:48:58,399 --> 01:49:00,001 CONTRAST OF CELLS IF THE SLOPE 2112 01:49:00,001 --> 01:49:02,137 IS MORE GENTLE IT'S LESS DEEP 2113 01:49:02,137 --> 01:49:04,706 THERE'LL BE A PROLONGED LIFE 2114 01:49:04,706 --> 01:49:08,143 SPAN OF INFECTED CELLS OR 2115 01:49:08,143 --> 01:49:10,478 INCREASED PRODUCTION OF RNA FOR 2116 01:49:10,478 --> 01:49:12,180 THE PER CELL BASIS. 2117 01:49:12,180 --> 01:49:13,782 AGAIN, THESE ARE MODELS WE 2118 01:49:13,782 --> 01:49:16,484 CAN -- AND I DON'T WANT TO SPEND 2119 01:49:16,484 --> 01:49:17,152 TOO MUCH TIME DISCUSSING THIS 2120 01:49:17,152 --> 01:49:23,958 BUT THESE ARE MODELS THAT CAN BE 2121 01:49:23,958 --> 01:49:24,793 VERY PRONE DO DISCUSSION BECAUSE 2122 01:49:24,793 --> 01:49:29,531 OF THE DISCUSSIONS MADE FROM THE 2123 01:49:29,531 --> 01:49:35,804 MATHEMATICAL POINT OF VIEW. 2124 01:49:35,804 --> 01:49:39,541 AND WE SHOWED THE DEPLETION OF 2125 01:49:39,541 --> 01:49:42,710 CD 8 T CELLS HAVE AN IMPACT ON 2126 01:49:42,710 --> 01:49:51,953 THE CURVE OF VIREMIA DECLINE. 2127 01:49:51,953 --> 01:49:54,656 AND THERE WERE 35 ANIMALS 2128 01:49:54,656 --> 01:49:59,093 DIVIDED IN THREE EXPERIMENTAL 2129 01:49:59,093 --> 01:50:02,664 GROUPS RECEIVING HETERODIMERIC 2130 01:50:02,664 --> 01:50:11,005 GROUP IN THE CONTROL ANIMALS. 2131 01:50:11,005 --> 01:50:21,516 THE MAIN RESULT YOU SEE WE'RE 2132 01:50:26,588 --> 01:50:33,695 DOING INITIAL ANALYSIS AND 2133 01:50:33,695 --> 01:50:36,364 AZD5582 IN COMBINATION DOES 2134 01:50:36,364 --> 01:50:39,300 EFFECT THE PRODUCTIVE INFECTED 2135 01:50:39,300 --> 01:50:43,037 CELLS AND IN FACT MAKES THE LIFE 2136 01:50:43,037 --> 01:50:43,338 SPAN LONGER. 2137 01:50:43,338 --> 01:50:45,673 THIS IS JUST FOCUSSING ON THE 2138 01:50:45,673 --> 01:50:46,274 INTERVENTION TIME FRAME. 2139 01:50:46,274 --> 01:50:51,913 ALSO IN THE STUDY WHEN YOU START 2140 01:50:51,913 --> 01:50:57,552 LOOKING AT THE RESERVOIR SIDE IN 2141 01:50:57,552 --> 01:51:00,054 BLOT AND LYMPH NODES 2142 01:51:00,054 --> 01:51:02,790 SEQUENTIALLY OVER TIME YOU SEE 2143 01:51:02,790 --> 01:51:11,366 THE ANIMALS RECEIVING AZD5582 2144 01:51:11,366 --> 01:51:16,204 AND A FASTER DECLINE OF THE 2145 01:51:16,204 --> 01:51:17,205 RESERVOIR COMPARED TO THE 2146 01:51:17,205 --> 01:51:19,140 CONTROL ANIMALS. 2147 01:51:19,140 --> 01:51:22,410 SO THERE IS -- THIS IS AN AFFECT 2148 01:51:22,410 --> 01:51:26,047 TRANSIENT BECAUSE AFTER 300 DAYS 2149 01:51:26,047 --> 01:51:29,550 IT'S NO LONGER SIGNIFICANT AND 2150 01:51:29,550 --> 01:51:34,122 AN ABILITY TO PERTURB THE 2151 01:51:34,122 --> 01:51:34,389 RESERVOIR. 2152 01:51:34,389 --> 01:51:36,190 THIS IS BY FOCUSSING ON THE 2153 01:51:36,190 --> 01:51:37,325 INITIAL PHASE OF THE STUDY. 2154 01:51:37,325 --> 01:51:41,062 THE STUDY IS BASICALLY ALMOST 2155 01:51:41,062 --> 01:51:41,429 FINISHED. 2156 01:51:41,429 --> 01:51:42,697 WE'RE STILL DOING SOME ANALYSIS 2157 01:51:42,697 --> 01:51:47,468 BUT THE KEY POINTS OF THIS 2158 01:51:47,468 --> 01:51:51,706 PARTICULAR COMBINATION OF 2159 01:51:51,706 --> 01:51:57,512 APPROACH IS AZD5582 ALONE OR 2160 01:51:57,512 --> 01:52:01,716 WITH HETERODIMERIC IL-15 INDUCES 2161 01:52:01,716 --> 01:52:06,187 A SLOWER DECLINE OF VIREMIA 2162 01:52:06,187 --> 01:52:14,262 WHICH MEANS INFECTED CELLS OR 2163 01:52:14,262 --> 01:52:16,931 VIRUS PRODUCTION AND THE 2164 01:52:16,931 --> 01:52:19,934 INTERVENTION PERTURBS THE 2165 01:52:19,934 --> 01:52:20,902 ESTABLISHMENT OF THE VIRUS 2166 01:52:20,902 --> 01:52:24,172 RESERVOIR FOR SEVERAL WEEKS. 2167 01:52:24,172 --> 01:52:28,309 IT DOES THAT IN LAB AND LYMPH 2168 01:52:28,309 --> 01:52:30,111 NODE AND HAS RATIONALE FOR 2169 01:52:30,111 --> 01:52:31,813 FURTHER EXPLORING THE MECHANISM 2170 01:52:31,813 --> 01:52:37,986 OF REVERSAL OF LATENCY WITH 2171 01:52:37,986 --> 01:52:40,088 ADDITIONAL INTERVENTIONS. 2172 01:52:40,088 --> 01:52:44,859 IT DOESN'T HAVE TO BE AZD5582 2173 01:52:44,859 --> 01:52:46,127 AND RECOGNIZE THE PROBLEMS GOING 2174 01:52:46,127 --> 01:52:47,662 WITH HUMANS IN THE COMPOUND AND 2175 01:52:47,662 --> 01:52:50,732 THE PANEL WAY TARGET REMAINS 2176 01:52:50,732 --> 01:52:50,965 VIABLE. 2177 01:52:50,965 --> 01:52:52,800 THIS IS THE STUDY WE'RE DOING 2178 01:52:52,800 --> 01:52:56,637 NOW IN WHICH BASICALLY WE'RE 2179 01:52:56,637 --> 01:53:01,876 TRYING TO ADD A COCKTAIL THE 2180 01:53:01,876 --> 01:53:07,315 SAME COCKTAIL OF NEUTRALIZING 2181 01:53:07,315 --> 01:53:09,183 SIV ENVELOPE SPECIFIC ANTIBODIES 2182 01:53:09,183 --> 01:53:10,885 AT THE TIME OF ART INITIATION. 2183 01:53:10,885 --> 01:53:14,222 THE IDEA IS TO INDUCE EITHER 2184 01:53:14,222 --> 01:53:18,159 MORE DRAMATIC PERTURBATION OF 2185 01:53:18,159 --> 01:53:20,161 THE ESTABLISHMENT OF THE 2186 01:53:20,161 --> 01:53:25,433 RESERVOIR BY A CLEARING 2187 01:53:25,433 --> 01:53:27,635 COMPOUND WITH THE LATENCY 2188 01:53:27,635 --> 01:53:27,902 REVERSAL. 2189 01:53:27,902 --> 01:53:30,171 WITH THIS I ACKNOWLEDGE IT'S 2190 01:53:30,171 --> 01:53:32,440 BEEN GREAT WORKING ONE OUR 2191 01:53:32,440 --> 01:53:34,142 WONDERFUL LEADER AND THE FORCE 2192 01:53:34,142 --> 01:53:38,646 BEHIND THE STUDY AND I WANT TO 2193 01:53:38,646 --> 01:53:43,384 EMPHASIZE VICTOR BECAUSE THIS 2194 01:53:43,384 --> 01:53:46,020 WHOLE THING TO ME IS SOMETHING I 2195 01:53:46,020 --> 01:53:46,721 STILL REMEMBER AS IT WAS 2196 01:53:46,721 --> 01:53:46,988 YESTERDAY. 2197 01:53:46,988 --> 01:53:57,331 THANK YOU VERY MUCH. 2198 01:54:26,694 --> 01:54:26,761 2199 01:54:26,761 --> 01:54:28,463 >> WE'RE DEFINING THE STRATEGIES 2200 01:54:28,463 --> 01:54:30,198 AS EFFICACIOUS AND WHETHER OR 2201 01:54:30,198 --> 01:54:32,166 NOT THEY MAKE CELLS ABLE TO BE 2202 01:54:32,166 --> 01:54:32,633 CLEARED. 2203 01:54:32,633 --> 01:54:36,938 AND FURTHER STUDIES HAVE 2204 01:54:36,938 --> 01:54:37,638 PERSISTENCE IN TISSUES. 2205 01:54:37,638 --> 01:54:40,708 THE HLE TARGETING APPROACH IS 2206 01:54:40,708 --> 01:54:46,414 BEING FURTHER TESTED IN BOTH THE 2207 01:54:46,414 --> 01:54:51,285 IN VIVO MODELS AND SO WE HAVE 2208 01:54:51,285 --> 01:54:53,154 SOME PRELIMINARY EVIDENCE THAT 2209 01:54:53,154 --> 01:54:54,789 WE'RE SEEKING OFF FURTHER WAYS 2210 01:54:54,789 --> 01:54:55,189 TO EXPAND. 2211 01:54:55,189 --> 01:54:58,159 WE HOPE THIS WILL BE AN 2212 01:54:58,159 --> 01:54:59,560 IMPORTANT WAY TO CLEAR CELLS. 2213 01:54:59,560 --> 01:55:02,630 ONE OF THE ASPECTS THAT GUIDO 2214 01:55:02,630 --> 01:55:05,533 JUST MENTIONED IS THE HOPE WE'LL 2215 01:55:05,533 --> 01:55:09,203 BE ABLE TO ADD AN EVALUATION OF 2216 01:55:09,203 --> 01:55:15,476 THIS HLAEVL9 ANTIBODY TO AUGMENT 2217 01:55:15,476 --> 01:55:16,611 CLEARANCE IN THE PRIMATE MODEL 2218 01:55:16,611 --> 01:55:19,080 LATER THIS YEAR. 2219 01:55:19,080 --> 01:55:25,753 AND THEN FINALLY OR CONTINUOUSLY 2220 01:55:25,753 --> 01:55:27,321 TO ASSESS THE SYSTEMS AND ASSESS 2221 01:55:27,321 --> 01:55:28,956 THE ADVANCES IN VIVO SYSTEMS AND 2222 01:55:28,956 --> 01:55:34,762 PREPARE THEM TO MOVE TO HUMAN 2223 01:55:34,762 --> 01:55:35,062 TESTING. 2224 01:55:35,062 --> 01:55:45,606 SO IN THAT REGARD CONTINUE AND 2225 01:55:47,708 --> 01:55:50,278 OUR CARE COLLABORATORY MOVED 2226 01:55:50,278 --> 01:55:52,446 FORWARD UNDER THE CLINIC AND THE 2227 01:55:52,446 --> 01:55:57,418 HOPE TO TEST MEMETIC IN THE LRA 2228 01:55:57,418 --> 01:55:58,653 PHASE 1 STUDY. 2229 01:55:58,653 --> 01:56:00,188 I THINK THESE ARE CHALLENGING 2230 01:56:00,188 --> 01:56:01,522 THING AND THINK THEY'LL COME UP 2231 01:56:01,522 --> 01:56:04,926 IN THE PANELS TOWARD THE END. 2232 01:56:04,926 --> 01:56:09,030 IT SHOULD BE RECOGNIZED THE IAP 2233 01:56:09,030 --> 01:56:11,999 MOLECULE WOULDN'T HAVE BEEN 2234 01:56:11,999 --> 01:56:17,271 DEVELOPED WITHOUT OUR 2235 01:56:17,271 --> 01:56:17,605 COLLABORATION. 2236 01:56:17,605 --> 01:56:19,941 AND FINALLY ANOTHER 2237 01:56:19,941 --> 01:56:21,609 COLLABORATION WITH MICROGENETICS 2238 01:56:21,609 --> 01:56:23,978 A COMPANY WORKING IN HIV AND HAS 2239 01:56:23,978 --> 01:56:26,414 SINCE LEFT THE FIELD BUT THE 2240 01:56:26,414 --> 01:56:27,048 MOLECULES THAT WERE DEVELOPED 2241 01:56:27,048 --> 01:56:28,816 THERE WERE TRYING TO HAVE A 2242 01:56:28,816 --> 01:56:31,252 PROOF OF CONCEPT STUDY WITH THEM 2243 01:56:31,252 --> 01:56:37,792 IN HUMANS AS WELL. 2244 01:56:37,792 --> 01:56:42,196 SO, AGAIN, AND OPEN FOR 2245 01:56:42,196 --> 01:56:52,373 QUESTIONS. 2246 01:56:55,042 --> 01:57:00,982 >> I GUESS IT COULD BE MORE 2247 01:57:00,982 --> 01:57:04,552 BROADLY ADDRESSED. 2248 01:57:04,552 --> 01:57:06,420 AND REGULATE LATENCY 2249 01:57:06,420 --> 01:57:07,989 HISTORICALLY HAVE USED 2250 01:57:07,989 --> 01:57:10,391 PROVIRUSES IN CELLS THAT HAVE 2251 01:57:10,391 --> 01:57:12,293 BEEN SELECTED TO BE EASED WITH 2252 01:57:12,293 --> 01:57:15,429 WHICH LATENCY IS REVERSED AND 2253 01:57:15,429 --> 01:57:17,832 THEN DO COMPLIMENTARY STUDIES 2254 01:57:17,832 --> 01:57:20,835 GOING TO PRIMARY CELLS WITH A 2255 01:57:20,835 --> 01:57:22,069 POPULATION OF PROVIRUSES AND 2256 01:57:22,069 --> 01:57:24,939 REPRESENT THE IN THE LATTER 2257 01:57:24,939 --> 01:57:25,573 EXPERIMENT IS A FOLD INCREASE IN 2258 01:57:25,573 --> 01:57:28,009 RNA. 2259 01:57:28,009 --> 01:57:31,712 BUT MY QUESTION IS IN THOSE 2260 01:57:31,712 --> 01:57:32,847 COMPLEMENTARY EXPERIMENTS WHAT 2261 01:57:32,847 --> 01:57:37,351 FRACTION OF THE PROVIRUSES ARE 2262 01:57:37,351 --> 01:57:41,222 BEING ACTIVATED. 2263 01:57:41,222 --> 01:57:43,124 THAT'S KEY IF IT'S 2% BUT IF 2264 01:57:43,124 --> 01:57:46,093 IT'S 99% WE ARE GETTING CLOSE. 2265 01:57:46,093 --> 01:57:48,763 DO YOU HAVE A SENSE OF WHAT 2266 01:57:48,763 --> 01:57:52,199 FRACTION OF PROVIRUSES ARE BEING 2267 01:57:52,199 --> 01:57:57,438 ACTIVATED BY THE GENES THAT 2268 01:57:57,438 --> 01:57:57,738 COMPLEMENT. 2269 01:57:57,738 --> 01:58:01,008 >> THE SHORT ANSWER IS NO, WE 2270 01:58:01,008 --> 01:58:01,208 DON'T. 2271 01:58:01,208 --> 01:58:04,245 I THINK IT'S A REASONABLE GUEST 2272 01:58:04,245 --> 01:58:06,080 THE RESERVOIR IS HETEROGENEOUS 2273 01:58:06,080 --> 01:58:08,115 HAVE GOT DIFFERENT STATES AND 2274 01:58:08,115 --> 01:58:09,817 DIFFERENT CELLS AND SOME CELLS 2275 01:58:09,817 --> 01:58:10,718 WILL BE LIMITING OTHERS NOT. 2276 01:58:10,718 --> 01:58:14,221 SO I THINK IT'S UNLIKELY ANY ONE 2277 01:58:14,221 --> 01:58:15,723 THING WILL BE IN ALL THE 2278 01:58:15,723 --> 01:58:16,290 RESERVOIR BROADLY. 2279 01:58:16,290 --> 01:58:18,526 I THINK THAT'S WHY WE HAVE TO GO 2280 01:58:18,526 --> 01:58:21,629 FOR A KITCHEN SINK MULTI-PRONGED 2281 01:58:21,629 --> 01:58:21,896 APPROACH. 2282 01:58:21,896 --> 01:58:26,400 IN TERMS OF FINDING WAYS TO LOOK 2283 01:58:26,400 --> 01:58:29,837 AT THAT THERE'S A SINGLE CELL 2284 01:58:29,837 --> 01:58:32,106 PROBE A WAY TO MEASURE THE SEQ. 2285 01:58:32,106 --> 01:58:33,574 THOSE ARE EXPENSIVE EXPERIMENTS 2286 01:58:33,574 --> 01:58:34,875 AS I'M SURE YOU KNOW. 2287 01:58:34,875 --> 01:58:36,444 THE ANSWER AT THIS POINT NO WE 2288 01:58:36,444 --> 01:58:39,647 DON'T BUT WOULD BE REALLY 2289 01:58:39,647 --> 01:58:39,914 IMPORTANT. 2290 01:58:39,914 --> 01:58:43,084 >> JUST A COMMENT. 2291 01:58:43,084 --> 01:58:46,020 IN JAY LEV CELLS WE LOOKED AT 2292 01:58:46,020 --> 01:58:48,823 REVERSE TRANSCRIPTASE ACTIVITY 2293 01:58:48,823 --> 01:58:51,592 ASSAY AND GFP WITHIN THE CELL 2294 01:58:51,592 --> 01:58:53,728 ALONE WE DO SEE THAT THERE ARE 2295 01:58:53,728 --> 01:58:56,497 HIGHER PERCENTAGE OF CELLS 2296 01:58:56,497 --> 01:58:58,032 ACTIVATED AND THEN ALMOST SEEMS 2297 01:58:58,032 --> 01:59:01,602 THE CELLS PRODUCING VIRUS MAY BE 2298 01:59:01,602 --> 01:59:04,405 PRODUCING MORE VIRUS. 2299 01:59:04,405 --> 01:59:07,241 SO I ASSUME THAT'S HAPPENING IN 2300 01:59:07,241 --> 01:59:08,576 THE PRIMARY CELLS AS WELL. 2301 01:59:08,576 --> 01:59:11,545 >> TO QUESTION YOUR QUESTION, I 2302 01:59:11,545 --> 01:59:12,380 GUESS I AGREE. 2303 01:59:12,380 --> 01:59:14,382 I THINK THIS IS A CHALLENGE FOR 2304 01:59:14,382 --> 01:59:18,152 THE FIELD AND I THINK WE MISSED 2305 01:59:18,152 --> 01:59:21,956 OPPORTUNITIES IN THE PAST BY 2306 01:59:21,956 --> 01:59:24,191 EXPECTING TOO MUCH FROM A SINGLE 2307 01:59:24,191 --> 01:59:25,960 DRUG OR GENE KNOCK DOWN OR 2308 01:59:25,960 --> 01:59:26,394 PATHWAY. 2309 01:59:26,394 --> 01:59:28,529 I THINK EVERYTHING WE TALKED 2310 01:59:28,529 --> 01:59:29,530 ABOUT THIS WEEK SHOWS THERE'S 2311 01:59:29,530 --> 01:59:31,966 MULTIPLE FACTORS THAT LEAD TO 2312 01:59:31,966 --> 01:59:33,701 PERSISTENT PROVIRAL INFECTION IN 2313 01:59:33,701 --> 01:59:36,003 DIFFERENT CELL POPULATIONS. 2314 01:59:36,003 --> 01:59:39,607 AND SO THE KITCHEN SINK IS PRO 2315 01:59:39,607 --> 01:59:41,675 ETCH IS HELPFUL SOMETIMES 2316 01:59:41,675 --> 01:59:42,610 BECAUSE YOU SEE A SIGNAL AND 2317 01:59:42,610 --> 01:59:44,779 THEN HAVE TO UNRAVEL IT. 2318 01:59:44,779 --> 01:59:49,116 AND I THINK WE'VE OFTEN IGNORED 2319 01:59:49,116 --> 01:59:51,819 PROMISING EFFECTS THAT ARE ONLY 2320 01:59:51,819 --> 01:59:53,187 TWO OR THREEFOLD INDUCTION AND 2321 01:59:53,187 --> 01:59:56,557 AS WE MOVE THEM FORWARD AND TEST 2322 01:59:56,557 --> 01:59:59,059 THEM IN OTHER MODELS OR COMBINE 2323 01:59:59,059 --> 02:00:00,761 THEM WITH OTHER THINGS WE 2324 02:00:00,761 --> 02:00:03,364 RECOGNIZE THEY MAY ACTUALLY BE 2325 02:00:03,364 --> 02:00:03,631 USEFUL. 2326 02:00:03,631 --> 02:00:05,933 I THINK IT'S A VERY DIFFICULT 2327 02:00:05,933 --> 02:00:10,371 AREA THAT CAN REALLY ONLY BE 2328 02:00:10,371 --> 02:00:12,173 MOVED FORWARD BY DIFFERENT 2329 02:00:12,173 --> 02:00:14,074 APPROACHES IN DIFFERENT MODELS 2330 02:00:14,074 --> 02:00:20,147 AND LOOKED AT HOLISTICALLY. 2331 02:00:20,147 --> 02:00:27,855 >> MY QUESTION IS FOR HUNGBING 2332 02:00:27,855 --> 02:00:32,326 AND I THINK OF CD 8 POSITIVE K 2333 02:00:32,326 --> 02:00:36,564 CELLS AND EXPANDED THE CELLS IN 2334 02:00:36,564 --> 02:00:39,366 THE PRESENCE OF PEPTIDES AND 2335 02:00:39,366 --> 02:00:43,037 THEY SEEM GET POOR RESPONSES. 2336 02:00:43,037 --> 02:00:45,539 I'M WONDERING ARE YOU USING THEM 2337 02:00:45,539 --> 02:00:49,376 WITHIN THE CD 8 T CELLS IS THAT 2338 02:00:49,376 --> 02:00:50,377 A MARKER YOU'RE FAMILIAR WITH ON 2339 02:00:50,377 --> 02:00:52,079 THE OTHER SIDE? 2340 02:00:52,079 --> 02:00:54,281 >> FOR ALL T CELL WORK WE ARE 2341 02:00:54,281 --> 02:00:57,551 VERY FOCUSSED ON THE CD 8 T 2342 02:00:57,551 --> 02:00:57,751 CELLS. 2343 02:00:57,751 --> 02:00:59,820 SO WHEN WE DO THE PRIMING OR 2344 02:00:59,820 --> 02:01:06,894 CLOTH WE DID DELIVERY TO EXCLUDE 2345 02:01:06,894 --> 02:01:07,995 NK CELLS. 2346 02:01:07,995 --> 02:01:12,566 AS THE NOT THE PATH WE HAVE 2347 02:01:12,566 --> 02:01:15,803 ADVOCATED AND SO BY CHALLENGE WE 2348 02:01:15,803 --> 02:01:19,640 HAVE THAT ONE OF THE NK GA 2349 02:01:19,640 --> 02:01:23,010 POSITIVE CLONES TO PASS 2350 02:01:23,010 --> 02:01:24,044 ANTIBODY. 2351 02:01:24,044 --> 02:01:27,748 BUT THE PRIMARY FUNCTION IS TOO 2352 02:01:27,748 --> 02:01:32,086 REGULATE NK CELLS. 2353 02:01:32,086 --> 02:01:33,053 THAT'S ALWAYS THE MAIN. 2354 02:01:33,053 --> 02:01:36,090 SO TO YOUR QUESTION, WE HAVEN'T 2355 02:01:36,090 --> 02:01:44,798 LOOKED AT THAT PART. 2356 02:01:44,798 --> 02:01:48,536 >> UNIVERSITY OF NEBRASKA. 2357 02:01:48,536 --> 02:01:59,046 QUESTION ABOUT THE PEPTIDE IS 2358 02:02:01,916 --> 02:02:04,051 CONSERVED CROSS DIFFERENT CLAY 2359 02:02:04,051 --> 02:02:14,194 OF HIV AND BETA SHOW THE IMPACT 2360 02:02:14,194 --> 02:02:18,666 PRESSURE ON THE VIRUS. 2361 02:02:18,666 --> 02:02:20,734 HAVE YOU OBSERVED THE ESCAPE 2362 02:02:20,734 --> 02:02:21,001 MUTATION. 2363 02:02:21,001 --> 02:02:22,269 >> SO FAR WE ONLY IDENTIFIED 2364 02:02:22,269 --> 02:02:29,109 THOSE THREE PEPTIDES. 2365 02:02:29,109 --> 02:02:36,216 THERE'S A B57 PEPTIDE AND THE 2366 02:02:36,216 --> 02:02:46,427 RAF IL-82 AND THE IL-9 IS HIGHLY 2367 02:02:46,427 --> 02:02:53,667 CONSERVE ED AND IT'S RELATIVELY 2368 02:02:53,667 --> 02:02:54,168 CONSERVED. 2369 02:02:54,168 --> 02:02:58,138 SO IN TERMS OF IMMUNE PRESSURE 2370 02:02:58,138 --> 02:03:02,376 FOR MUTATION WE DON'T KNOW YET. 2371 02:03:02,376 --> 02:03:08,582 THAT'S SOMETHING WE WANT TO 2372 02:03:08,582 --> 02:03:08,882 INVESTIGATE. 2373 02:03:08,882 --> 02:03:10,751 AND WHEN WE DO EXPRESSION ASSAY. 2374 02:03:10,751 --> 02:03:15,322 IN VITRO FIVE DAYS, SIX DAYS 2375 02:03:15,322 --> 02:03:17,625 MAYBE NOT LONG ENOUGH TO DRIVE 2376 02:03:17,625 --> 02:03:19,560 MUTATION BUT SAY IN THE FUTURE 2377 02:03:19,560 --> 02:03:23,597 THE IN VIVO MODEL THEN WE CAN 2378 02:03:23,597 --> 02:03:26,233 LOOK AT THOSE. 2379 02:03:26,233 --> 02:03:30,537 IF THEY GIVE PRESSURE ENOUGH. 2380 02:03:30,537 --> 02:03:32,973 THANKS. 2381 02:03:32,973 --> 02:03:43,517 >> GUIDO, SHAURN SHED COMPELLING 2382 02:03:44,318 --> 02:03:54,795 DATA YESTERDAY AND STARTING AND 2383 02:04:02,302 --> 02:04:07,241 CORRELATED EFFECTS. 2384 02:04:07,241 --> 02:04:17,785 >> IT'S POSSIBLE AND DEPLETION 2385 02:04:21,288 --> 02:04:23,090 SEEMS LIKE THE STRAIGHTFORWARD 2386 02:04:23,090 --> 02:04:30,230 INTERVENTION AND IT'S 2387 02:04:30,230 --> 02:04:32,433 MULTI-FACTORIAL AND IT'S 2388 02:04:32,433 --> 02:04:37,204 POSSIBLE THERE IS APE EFFECT 2389 02:04:37,204 --> 02:04:40,007 LIKE THAT THAT JUSTIFIES THE 2390 02:04:40,007 --> 02:04:40,908 KINETIC OF VIRAL DECLINE. 2391 02:04:40,908 --> 02:04:44,411 ONE THING TO KEEP IN MIND IS 2392 02:04:44,411 --> 02:04:47,915 THAT REALLY THE ULTIMATE READ 2393 02:04:47,915 --> 02:04:48,749 OUT OF THE STUDY IS THE 2394 02:04:48,749 --> 02:04:52,720 RESERVOIR THE NUMBER OF YELLS 2395 02:04:52,720 --> 02:04:56,890 THAT ARE ENTERING THE PERSISTENT 2396 02:04:56,890 --> 02:05:03,130 RESERVOIR WITH REPLICATION 2397 02:05:03,130 --> 02:05:04,064 PRESUMABLY PROVIDERS. 2398 02:05:04,064 --> 02:05:10,370 MY REASONING IS IF IS JUST A 2399 02:05:10,370 --> 02:05:16,009 SIMPLE LOOK OF KILLING BY THE CD 2400 02:05:16,009 --> 02:05:18,879 8 CELLS BECAUSE THEIR NATURE AND 2401 02:05:18,879 --> 02:05:21,949 MICROBIOLOGY STUDY SHOULD NOT 2402 02:05:21,949 --> 02:05:24,184 HAVE IMPACT ON THE RESERVOIR 2403 02:05:24,184 --> 02:05:24,885 SIZE. 2404 02:05:24,885 --> 02:05:27,087 THERE'S AN IMPACT ON THE 2405 02:05:27,087 --> 02:05:32,426 RESERVOIR SIZE IT'S AN EFFECT 2406 02:05:32,426 --> 02:05:33,527 DISTINCT FROM THE CD 8 2407 02:05:33,527 --> 02:05:33,961 IMPAIRMENT. 2408 02:05:33,961 --> 02:05:39,600 OTHERWISE YOU HAVE TO PREDICATE 2409 02:05:39,600 --> 02:05:42,836 ACTIVITY ON THE CD IS MORE 2410 02:05:42,836 --> 02:05:48,475 POWERFUL THAN CD 8 DEPLETION 2411 02:05:48,475 --> 02:05:58,619 ITSELF. 2412 02:06:14,134 --> 02:06:16,637 >> YOU HAVE INFECTION OF THE 2413 02:06:16,637 --> 02:06:25,245 TARGET AND IMMUNO RERECTORY -- 2414 02:06:25,245 --> 02:06:26,413 IMMUNOREGULATORY EFFECTS AND 2415 02:06:26,413 --> 02:06:32,019 THERE'S MULTIPLE COMPONENTS TO 2416 02:06:32,019 --> 02:06:42,296 THEIR ACTIVITY. 2417 02:06:50,437 --> 02:06:52,739 WE SAW WITH THE mRNA VACCINE 2418 02:06:52,739 --> 02:06:56,076 CONTROL YOU MIGHT ENHANCE YOUR 2419 02:06:56,076 --> 02:06:56,977 INCREASE SET POINT. 2420 02:06:56,977 --> 02:06:59,746 I THINK IN MOST OF YOUR STUDIES 2421 02:06:59,746 --> 02:07:01,882 TODAY YOU HAVEN'T DONE ANY 2422 02:07:01,882 --> 02:07:07,654 TREATMENT INTERRUPTIONS IS THAT 2423 02:07:07,654 --> 02:07:07,855 RIGHT? 2424 02:07:07,855 --> 02:07:09,423 THAT PLAY BE AN IMPORTANT 2425 02:07:09,423 --> 02:07:09,990 FACTOR. 2426 02:07:09,990 --> 02:07:11,124 >> I DISAGREE AND WE CAN ARGUE 2427 02:07:11,124 --> 02:07:12,593 ABOUT THIS ALL THE TIME. 2428 02:07:12,593 --> 02:07:13,594 THE PRIMARY POINT OF THIS STUDY 2429 02:07:13,594 --> 02:07:18,265 IS TO LOOK AT THE EFFECT ON REZ 2430 02:07:18,265 --> 02:07:19,566 RESERVOIR SIZE AFTER THE 2431 02:07:19,566 --> 02:07:24,538 INTERVENTION AND YOU LOSE THE 2432 02:07:24,538 --> 02:07:27,674 ABILITY TO MEASURE THAT. 2433 02:07:27,674 --> 02:07:33,313 IF WE THINK WE'RE CLOSE TO A 2434 02:07:33,313 --> 02:07:36,283 CURE THEN TREATMENT INTERRUPTION 2435 02:07:36,283 --> 02:07:38,685 STUDIES ARE GREAT BUT IT'S 2436 02:07:38,685 --> 02:07:44,324 SIMILAR TO THE LOVELY STUDY WITH 2437 02:07:44,324 --> 02:07:50,430 THE VACCINE I'M INTERESTED TO 2438 02:07:50,430 --> 02:07:52,699 SEE WHAT THE FREQUENCY OF 2439 02:07:52,699 --> 02:07:53,533 PERSISTENT INFECTION IS AT THE 2440 02:07:53,533 --> 02:08:04,077 END OF ALL THESE INTERVENTIONS. 2441 02:08:06,013 --> 02:08:07,714 THEN CAN WE MEASURE IMMUNE 2442 02:08:07,714 --> 02:08:08,782 RESPONSES SUFFICIENT ENOUGH 2443 02:08:08,782 --> 02:08:13,053 THEY'LL BE GOOD ENOUGH TO ALTER 2444 02:08:13,053 --> 02:08:14,054 AN ATI. 2445 02:08:14,054 --> 02:08:15,989 IF YOU CONVINCE GUIDO NOW TO DO 2446 02:08:15,989 --> 02:08:18,025 A TREATMENT INTERRUPTION WE'LL 2447 02:08:18,025 --> 02:08:22,396 LOSE ALL THE DATA FROM THE STUDY 2448 02:08:22,396 --> 02:08:32,539 WE HAVE. 2449 02:08:39,513 --> 02:08:40,580 >> IS IT SUFFICIENT TO CHANGE 2450 02:08:40,580 --> 02:08:46,420 THE REBOUND AND THINGS LIKE 2451 02:08:46,420 --> 02:08:49,790 THAT. 2452 02:08:49,790 --> 02:08:52,993 IL COMES DOWN TO PRODUCT 2453 02:08:52,993 --> 02:08:54,161 DEVELOPMENT AND ANSWERING 2454 02:08:54,161 --> 02:08:55,195 SCIENTIFIC QUESTIONS. 2455 02:08:55,195 --> 02:08:58,498 I'M MORE IN THE SECOND CAMP BUT 2456 02:08:58,498 --> 02:08:59,700 MAYBE I'M WRONG. 2457 02:08:59,700 --> 02:09:01,301 >> I TOTALLY UNDERSTAND WHAT 2458 02:09:01,301 --> 02:09:02,302 YOU'RE SAYING, DAVID. 2459 02:09:02,302 --> 02:09:04,972 THE POINT IS IF THERE IS AN 2460 02:09:04,972 --> 02:09:06,707 ADVERSE EFFECT ON THE CD 8 2461 02:09:06,707 --> 02:09:12,145 CONTROL YOU MIGHT NOT SEE IT 2462 02:09:12,145 --> 02:09:12,813 WITHOUT YUPT RUMPS AND DO THESE 2463 02:09:12,813 --> 02:09:14,948 INNING MONKEYS. 2464 02:09:14,948 --> 02:09:17,351 THEY'RE A GREAT AVENUE. 2465 02:09:17,351 --> 02:09:21,188 >> IT DEPENDS ON HOW DURABLE AND 2466 02:09:21,188 --> 02:09:21,822 REVERSIBLE IT IS LIKE MANY DRUGS 2467 02:09:21,822 --> 02:09:24,057 WE USE IN MEDICINE ALL THE TIME. 2468 02:09:24,057 --> 02:09:26,393 WE USE DRUGS FOR DEFINED PERIOD 2469 02:09:26,393 --> 02:09:29,563 OF TIME AND WITHDRAW IT AND WE 2470 02:09:29,563 --> 02:09:34,401 HAVE TO WORRY ABOUT ALL THOSE 2471 02:09:34,401 --> 02:09:37,938 THINGS AN TEST AND SEE THEM. 2472 02:09:37,938 --> 02:09:46,947 >> WE'RE IN OUR COFFEE BREAK. 2473 02:09:46,947 --> 02:09:48,348 THANK YOU VERY MUCH FOR A GREAT 2474 02:09:48,348 --> 02:09:49,116 DISCUSSION. 2475 02:09:49,116 --> 02:09:52,085 IT'S A GOOD SEGUE TO CLEAR THE 2476 02:09:52,085 --> 02:09:53,253 PANEL DISCUSSION AFTER THE BREAK 2477 02:09:53,253 --> 02:09:57,858 PLEASE COME BACK PROMPTLY AT 2478 02:09:57,858 --> 02:09:58,058 11:00. 2479 02:09:58,058 --> 02:10:00,794 THERE SHOULD BE A COFFEE BREAK 2480 02:10:00,794 --> 02:10:03,929 SET UP AND IF YOU HAVE A POSTER 2481 02:10:03,929 --> 02:10:04,096 PLEASE REMOVE IT DURING THE 2482 02:10:04,096 --> 02:10:06,050 BREAK. THANK YOU. 2483 02:10:06,050 --> 02:10:07,051 OKAY. 2484 02:10:07,051 --> 02:10:08,620 LET'S GET STARTED WITH THIS 2485 02:10:08,620 --> 02:10:08,920 DISCUSSION. 2486 02:10:08,920 --> 02:10:10,555 WE HAVE TWO PAMS. 2487 02:10:10,555 --> 02:10:13,424 THE FIRST PANEL WILL BE TALKING 2488 02:10:13,424 --> 02:10:17,996 ABOUT TRANSLATING HIV CURES 2489 02:10:17,996 --> 02:10:25,270 STRATEGIES TO THE CLINIC AND 2490 02:10:25,270 --> 02:10:26,271 IT'S GOOD HAVE A PANEL 2491 02:10:26,271 --> 02:10:28,373 DISCUSSION AND THE TOPIC LIKE I 2492 02:10:28,373 --> 02:10:31,409 SAID IS TRANSLATING HIV CURE 2493 02:10:31,409 --> 02:10:34,646 STRATEGIES TO THE CLINIC. 2494 02:10:34,646 --> 02:10:35,713 DISCOVERIES ARE MADE IN CURES 2495 02:10:35,713 --> 02:10:36,748 STRATEGY BOUGHT BECAUSE THE 2496 02:10:36,748 --> 02:10:39,651 CULTURE AND COMMITMENT NEEDED TO 2497 02:10:39,651 --> 02:10:41,486 TRANSLATE TO CLINICAL TRIALS IS 2498 02:10:41,486 --> 02:10:42,287 LOOKING. 2499 02:10:42,287 --> 02:10:44,956 WE TASK THE PEOPLE ON THE PANEL 2500 02:10:44,956 --> 02:10:47,692 TO TELL US HOW TO PROPEL 2501 02:10:47,692 --> 02:10:48,493 INNOVATIVE RESEARCH OUT OF THE 2502 02:10:48,493 --> 02:10:50,595 LAB AND INTO THE CLINIC TO 2503 02:10:50,595 --> 02:10:52,830 IMPROVE THE LIVES OF PEOPLE 2504 02:10:52,830 --> 02:10:53,731 LIVING WITH HIV. 2505 02:10:53,731 --> 02:10:55,400 DR. STEVE DEEKS HAS AGREED TO BE 2506 02:10:55,400 --> 02:10:56,167 THE CHAIR OF THE SESSION. 2507 02:10:56,167 --> 02:11:02,540 I'LL HAND IT OVER TO HIM. 2508 02:11:02,540 --> 02:11:03,408 >> GREAT. 2509 02:11:03,408 --> 02:11:03,675 THANK YOU. 2510 02:11:03,675 --> 02:11:05,810 THIS IS A TOPIC I FEEL A LOT OF 2511 02:11:05,810 --> 02:11:06,377 PASSION ABOUT. 2512 02:11:06,377 --> 02:11:13,618 HOPEFULLY WE'LL GET A GOOD 2513 02:11:13,618 --> 02:11:16,487 DISCUSSION GOING AND STEVEN 2514 02:11:16,487 --> 02:11:17,522 DEEKS DOING CLINICAL TRIALS IN 2515 02:11:17,522 --> 02:11:20,024 THIS RELATED AREA FOR SOME TIME 2516 02:11:20,024 --> 02:11:22,660 AND CO-CHAIRING THIS WITH SANDY. 2517 02:11:22,660 --> 02:11:25,063 WE'LL INTRODUCE OURSELVES AN 2518 02:11:25,063 --> 02:11:27,432 SECOND AND THE LET ME GIVE 2519 02:11:27,432 --> 02:11:34,472 BEFORE PERSPECTIVE HERE. 2520 02:11:34,472 --> 02:11:35,907 I THINK THE HIV ESTABLISHMENT 2521 02:11:35,907 --> 02:11:42,080 AND COLLABORATORIES DO AN 2522 02:11:42,080 --> 02:11:45,617 OUTSTANDING JOB OF IDENTIFYING 2523 02:11:45,617 --> 02:11:47,819 UNIQUE AND INNOVATIVE STRATEGIES 2524 02:11:47,819 --> 02:11:52,323 FROM THE PETRI DISH THROUGH THE 2525 02:11:52,323 --> 02:11:54,726 PRE-WHEN I CAL MODELS INCLUDING 2526 02:11:54,726 --> 02:11:56,227 MOUSE AND MACAQUE MODELS. 2527 02:11:56,227 --> 02:12:01,499 WE HAVE DONE A GREAT JOB IN 2528 02:12:01,499 --> 02:12:03,001 IDENTIFYING POTENTIAL 2529 02:12:03,001 --> 02:12:08,773 INTERVENTIONS THAT CAN LEAD TO 2530 02:12:08,773 --> 02:12:11,709 DURABLE CONTROL OR CURE ON THE 2531 02:12:11,709 --> 02:12:15,146 OTHER HAND I THINK WE'RE OKAY OF 2532 02:12:15,146 --> 02:12:19,917 REPURPOSING ESTABLISHED DRUGS IN 2533 02:12:19,917 --> 02:12:30,161 PROOF OF CONCEPT OF STUDIES AND 2534 02:12:30,161 --> 02:12:32,897 GATES AND MHRP. 2535 02:12:32,897 --> 02:12:38,736 WHAT WE'RE NOT GOOD AT IS THE 2536 02:12:38,736 --> 02:12:40,305 PART IN THE MIDDLE OF TAKING 2537 02:12:40,305 --> 02:12:48,246 NOVEL DRUGS AND MOLECULES AND 2538 02:12:48,246 --> 02:12:54,319 ASSETS WHERE THAT THERE'S NO 2539 02:12:54,319 --> 02:12:55,053 EXISTING DRUGS BECAUSE IN THAT 2540 02:12:55,053 --> 02:12:56,521 PARTICULAR VALLEY THE WORK IS 2541 02:12:56,521 --> 02:13:06,964 NOT ACADEMICS CAN DO AND 2542 02:13:08,099 --> 02:13:11,836 RESOURCE INTENSIVE AND GO SOUP 2543 02:13:11,836 --> 02:13:13,604 TO NUTS HOW TO GET THINGS FROM 2544 02:13:13,604 --> 02:13:24,048 THE IDEAS INTO THE CLINIC. 2545 02:13:26,684 --> 02:13:28,419 WHAT THE NEEDS ARE IN TERMS OF 2546 02:13:28,419 --> 02:13:29,587 DEVELOPING NEW PRODUCTS AND HOW 2547 02:13:29,587 --> 02:13:35,193 THE NETWORKS WILL WORK TO 2548 02:13:35,193 --> 02:13:39,497 DEVELOP THE STUFF AND COME UP 2549 02:13:39,497 --> 02:13:41,566 WITH SOLUTIONS FOR THE ISSUES. 2550 02:13:41,566 --> 02:13:42,700 >> ANY THOUGHTS? 2551 02:13:42,700 --> 02:13:44,669 >> THANKS, STEVE. 2552 02:13:44,669 --> 02:13:51,142 I'M SANDY VASAN I CONDUCT THE 2553 02:13:51,142 --> 02:13:56,214 MILITARY HIV RESEARCH PROGRAM. 2554 02:13:56,214 --> 02:14:02,553 WE DO SPEND TIME WHERE STEVE 2555 02:14:02,553 --> 02:14:03,821 REFERENCED THE VALLEY OF DEATH 2556 02:14:03,821 --> 02:14:07,658 WHERE WE TAKE IDEAS FROM THE 2557 02:14:07,658 --> 02:14:10,795 PRECLINICAL SPACE AND MOVE THEM 2558 02:14:10,795 --> 02:14:13,297 FORWARD TO POPULATIONS NEEDED 2559 02:14:13,297 --> 02:14:13,664 MOST. 2560 02:14:13,664 --> 02:14:16,667 THE MDCs HAVE BEEN GREAT IN THE 2561 02:14:16,667 --> 02:14:19,203 LATEST ROUND WITH SO MANY 2562 02:14:19,203 --> 02:14:20,905 COLLABORATORIES LETTING A 2563 02:14:20,905 --> 02:14:22,774 THOUSAND FLOWERS BLOOM AND CAN 2564 02:14:22,774 --> 02:14:24,242 SEE THE SYNERGY ACROSS 2565 02:14:24,242 --> 02:14:25,176 COLLABORATORIES BUT HOW DO WE 2566 02:14:25,176 --> 02:14:31,516 GET TO THE PAINFUL PARTS OF DOWN 2567 02:14:31,516 --> 02:14:34,619 SELECTING THOSE THAT NEED THE 2568 02:14:34,619 --> 02:14:35,853 INVESTMENT IN MOVING FORWARD 2569 02:14:35,853 --> 02:14:39,223 THROUGH THE VALLEY OF DEATH AND 2570 02:14:39,223 --> 02:14:40,358 UNGLAMOROUS THINGS SUCH AS 2571 02:14:40,358 --> 02:14:45,930 TOXICITY TESTING AND STABILITY 2572 02:14:45,930 --> 02:14:48,633 AND RELEASE AND THINGS THAT ARE 2573 02:14:48,633 --> 02:14:50,268 LESS FUN OF LOOKING AT GRAPHS OF 2574 02:14:50,268 --> 02:14:54,639 VIRAL DECAY. 2575 02:14:54,639 --> 02:14:55,440 THOSE ARE THINGS WE'VE CALLED 2576 02:14:55,440 --> 02:15:01,312 OUR PANELISTS IN TO ANSWER. 2577 02:15:01,312 --> 02:15:09,287 ONE MORE NOTE. 2578 02:15:09,287 --> 02:15:11,789 WHEN WE THINK OF THE INFANTS, 2579 02:15:11,789 --> 02:15:14,258 CHILDREN AND ADOLESCENTS WHEN WE 2580 02:15:14,258 --> 02:15:15,793 THINK OF TRANSLATING STRATEGIES 2581 02:15:15,793 --> 02:15:19,397 TO BE TESTED IN THOSE VERY 2582 02:15:19,397 --> 02:15:23,434 SPECIAL POPULATIONS IT ADDS 2583 02:15:23,434 --> 02:15:26,971 REGULATORY HURDLES AND NOT JUST 2584 02:15:26,971 --> 02:15:31,042 DEVELOPMENT HURDLES BUT SPECIFIC 2585 02:15:31,042 --> 02:15:34,078 CONSIDERATIONS AND WE WERE 2586 02:15:34,078 --> 02:15:34,645 REMINISCING OF HOW 2587 02:15:34,645 --> 02:15:35,446 ANTIRETROVIRAL THERAPY HOW 2588 02:15:35,446 --> 02:15:37,081 DIFFICULT IT WAS FOR CHILDREN TO 2589 02:15:37,081 --> 02:15:40,017 TAKE THEIR ART MEDS BECAUSE SO 2590 02:15:40,017 --> 02:15:42,453 FEW WERE AVAILABLE FOR 2591 02:15:42,453 --> 02:15:44,222 SPECIFICALLY FOR CHILDREN AND 2592 02:15:44,222 --> 02:15:46,491 THOSE THAT HAD AWFUL TASTES, 2593 02:15:46,491 --> 02:15:52,029 POOR FORMULATIONS. 2594 02:15:52,029 --> 02:16:02,340 IT WAS DIFFICULT. 2595 02:16:15,052 --> 02:16:18,956 OVER TO YOU. 2596 02:16:18,956 --> 02:16:22,293 >> WHAT ARE THE INTERVENTION 2597 02:16:22,293 --> 02:16:25,763 STRATEGIES IN THE CLINIC AND GO 2598 02:16:25,763 --> 02:16:28,299 DOWN THE LINE AND ASK KATIE TO 2599 02:16:28,299 --> 02:16:31,435 PONTIFICATE FROM ZOOM LAND. 2600 02:16:31,435 --> 02:16:36,607 >> I'M MARINA CASKEY AT 2601 02:16:36,607 --> 02:16:41,379 ROCKEFELLER AND KATIE IS GOING 2602 02:16:41,379 --> 02:16:44,949 TO BE THE NEXT AND I HAVE 2603 02:16:44,949 --> 02:16:45,550 EXPERIENCED BRINGING STUDIES 2604 02:16:45,550 --> 02:16:52,590 INTO THE CLINIC FROM THEA CT 2605 02:16:52,590 --> 02:16:54,125 PERSPECTIVE AND STUDIES 2606 02:16:54,125 --> 02:16:55,459 INDEPENDENTLY AT ROCKEFELLER. 2607 02:16:55,459 --> 02:16:56,027 I HAVE SOME OPINIONS ABOUT 2608 02:16:56,027 --> 02:17:03,501 THOSE. 2609 02:17:03,501 --> 02:17:10,508 MOST MY WORK HAS BEEN WITH BNAB 2610 02:17:10,508 --> 02:17:14,946 AND A KEY HURDLE IS ACCESS TO 2611 02:17:14,946 --> 02:17:17,281 THE STUDY PRODUCTS. 2612 02:17:17,281 --> 02:17:20,251 I THINK NOT ONLY THE NOVEL STUDY 2613 02:17:20,251 --> 02:17:22,653 PRODUCTS THAT HAVE TO BE 2614 02:17:22,653 --> 02:17:23,955 MANUFACTURED THE FIRST LOT TO 2615 02:17:23,955 --> 02:17:27,425 TOXICITY TESTING AND REGULATORY, 2616 02:17:27,425 --> 02:17:29,160 ETCETERA BUT EVEN REPURPOSED 2617 02:17:29,160 --> 02:17:29,760 DRUGS. 2618 02:17:29,760 --> 02:17:30,561 IT'S NOT SO STRAIGHTFORWARD 2619 02:17:30,561 --> 02:17:34,665 BECAUSE THEY HAVE HIGH COST. 2620 02:17:34,665 --> 02:17:37,001 SOMETIMES THE FUNDING MECHANISMS 2621 02:17:37,001 --> 02:17:38,169 DO NOT ALLOW. 2622 02:17:38,169 --> 02:17:39,770 EITHER YOU DON'T HAVE THE 2623 02:17:39,770 --> 02:17:41,939 PARTNERSHIP WITH INDUSTRY YOU 2624 02:17:41,939 --> 02:17:44,141 HOPE TO HAVE IF THEY'RE NOT 2625 02:17:44,141 --> 02:17:47,178 ALREADY INVOLVED IN THE HIV 2626 02:17:47,178 --> 02:17:52,683 FIELD AND EVEN IF THE DRUGS THE 2627 02:17:52,683 --> 02:17:55,486 PURCHASE CAN BE HIGH AND FUNDING 2628 02:17:55,486 --> 02:18:03,427 MECHANISMS CAN BE LIMITING. 2629 02:18:03,427 --> 02:18:06,897 YOU ASKED ME HOW WERE YOU ARE 2630 02:18:06,897 --> 02:18:11,302 ABLE TO DO THEY WILL AU -- ALL 2631 02:18:11,302 --> 02:18:16,407 THE STUDIES AND THEY'VE BEEN 2632 02:18:16,407 --> 02:18:17,908 THROUGH DIFFERENT TYPES OF 2633 02:18:17,908 --> 02:18:19,176 PHILANTHROPY AND GAVE US THE 2634 02:18:19,176 --> 02:18:22,113 OPPORTUNITY TO DO STUDIES WE DID 2635 02:18:22,113 --> 02:18:26,517 AND PARTNER AND PROVIDE OR HAVE 2636 02:18:26,517 --> 02:18:31,322 ACCESS FOR INVESTIGATION 2637 02:18:31,322 --> 02:18:41,065 UNDERSTANDING THE TWO TO ENABLE 2638 02:18:41,065 --> 02:18:47,438 NEW LOTS TO BE PRODUCED WITH YOU 2639 02:18:47,438 --> 02:18:52,076 KEYS THE STUDIES ARE NOT SIMPLE. 2640 02:18:52,076 --> 02:18:58,716 IT'S REALLY DIFFICULT TO RECRUIT 2641 02:18:58,716 --> 02:18:59,050 PARTICIPANTS. 2642 02:18:59,050 --> 02:19:05,122 WE'RE ASKING A LOT FROM AND 2643 02:19:05,122 --> 02:19:06,123 STEPPING FORWARD IN THE RESEARCH 2644 02:19:06,123 --> 02:19:08,092 AND THE INVESTIGATORS AND GROUPS 2645 02:19:08,092 --> 02:19:10,461 AND SITES THAT REALLY HAVE THE 2646 02:19:10,461 --> 02:19:12,930 APPETITE TO EMBARK IN THESE 2647 02:19:12,930 --> 02:19:14,899 CHALLENGING STUDIES TO NOT ONLY 2648 02:19:14,899 --> 02:19:16,100 LAUNCH BUT CARRY OUT. 2649 02:19:16,100 --> 02:19:17,435 AND ALL THE SAMPLE COLLECTIONS 2650 02:19:17,435 --> 02:19:24,175 IN PARTNERSHIPS WITH VARIOUS 2651 02:19:24,175 --> 02:19:26,410 COLLEAGUES AND LOOK AT THIS FROM 2652 02:19:26,410 --> 02:19:27,945 VARIOUS ANGLES AND WE HAVE TO 2653 02:19:27,945 --> 02:19:28,713 COME TOGETHER AND UNDERSTAND WE 2654 02:19:28,713 --> 02:19:30,114 HAVE TO HAVE A WHOLESOME 2655 02:19:30,114 --> 02:19:30,681 UNDERSTANDING OF WHAT THE 2656 02:19:30,681 --> 02:19:37,021 INTERVENTIONS MAY BE DOING. 2657 02:19:37,021 --> 02:19:39,623 NOT RELYING ON ONLY STANDARD 2658 02:19:39,623 --> 02:19:42,560 ASSAYS AND LOOKING AT 2659 02:19:42,560 --> 02:19:43,127 INTERESTING SIGNALS IN GENT 2660 02:19:43,127 --> 02:19:49,300 STUDIES. 2661 02:19:49,300 --> 02:19:55,139 I'M THE CO-P.I. FOR THE 2662 02:19:55,139 --> 02:19:58,275 COLLABORATORY AND CHAIR FOR THE 2663 02:19:58,275 --> 02:20:00,211 SCIENTIFIC COMMITTEE. 2664 02:20:00,211 --> 02:20:02,613 I WANT TO THANK THE NIH FOR 2665 02:20:02,613 --> 02:20:03,948 FUNDING A PEDIATRIC PURE AGENDA. 2666 02:20:03,948 --> 02:20:07,852 THE BAR IS HIGH FOR PEDIATRICS 2667 02:20:07,852 --> 02:20:09,386 WHEN WE TALK ABOUT INTERVENTIONS 2668 02:20:09,386 --> 02:20:10,788 IT'S IMPORTANT TO REMIND THE 2669 02:20:10,788 --> 02:20:12,890 AUDIENCE A BABY WITH HIV DOES 2670 02:20:12,890 --> 02:20:23,434 BECOME AN ADULT AND CAN LIVE TO 2671 02:20:23,667 --> 02:20:25,536 THE FOURTH DECADE OF LIFE AND 2672 02:20:25,536 --> 02:20:27,138 IT'S IMPORTANT TO THINK HOW THE 2673 02:20:27,138 --> 02:20:28,305 STRATEGIES CAN BE APPLIED ACROSS 2674 02:20:28,305 --> 02:20:33,344 THE AIDS SPECTRUM AND WITH 2675 02:20:33,344 --> 02:20:34,512 UNIQUE CONSIDERATIONS FOR 2676 02:20:34,512 --> 02:20:35,913 DEVELOPING THE IMMUNE SYSTEM IN 2677 02:20:35,913 --> 02:20:41,385 WHICH THE RESERVOIR IS 2678 02:20:41,385 --> 02:20:41,685 ESTABLISHED. 2679 02:20:41,685 --> 02:20:44,054 I HOPE YESTERDAY YOU GOT A 2680 02:20:44,054 --> 02:20:47,324 FLAVOR FOR DISTINCT FEATURES OF 2681 02:20:47,324 --> 02:20:48,292 INFECTION TO A PLACE OF 2682 02:20:48,292 --> 02:20:50,227 REMISSION AND CURE. 2683 02:20:50,227 --> 02:20:55,733 I'LL START WITH A RETROSPECTIVE 2684 02:20:55,733 --> 02:21:06,277 LOOK AND WE DIDN'T KNOW HOW TO 2685 02:21:08,546 --> 02:21:15,452 DOSE IN NEWBORNS ONLY FOR 2686 02:21:15,452 --> 02:21:17,488 PROPHYLAXIS AND IT'S HOW MANY 2687 02:21:17,488 --> 02:21:21,625 REGIMENTS LAG BEHIND ADULTS. 2688 02:21:21,625 --> 02:21:28,065 IT'S ONLY TWO AND THE STAYED ON 2689 02:21:28,065 --> 02:21:29,800 IT FIVE YEARS BEFORE WE STOPPED 2690 02:21:29,800 --> 02:21:30,234 DRUG TREATMENT. 2691 02:21:30,234 --> 02:21:35,439 ONE MAIN HURDLE IS INVESTMENT IN 2692 02:21:35,439 --> 02:21:39,944 BASIC EFFECTIVE DRUGS FOR 2693 02:21:39,944 --> 02:21:48,419 CHILDREN IF WE HAVEN'T CURED WE 2694 02:21:48,419 --> 02:21:55,092 ED ACCESS FOR TREATMENT AND 2695 02:21:55,092 --> 02:21:55,659 YOUNG ADOLESCENT TREATMENT. 2696 02:21:55,659 --> 02:21:59,797 THE MAJOR HURDLE IS INDUSTRY 2697 02:21:59,797 --> 02:22:00,931 INVESTMENT IN OUR AGENDA AND 2698 02:22:00,931 --> 02:22:03,100 DELIVERY OF PRODUCTS WE BELIEVE 2699 02:22:03,100 --> 02:22:05,769 COULD HAVE DIFFERENT OUTCOMES IN 2700 02:22:05,769 --> 02:22:07,705 THE PEDIATRIC SETTING WHERE THE 2701 02:22:07,705 --> 02:22:09,039 RESERVOIR IS LOW. 2702 02:22:09,039 --> 02:22:11,075 IT'S LOW DIVERSITY AND WHERE THE 2703 02:22:11,075 --> 02:22:13,544 IMMUNE SYSTEM IS A CLEAN SLATE 2704 02:22:13,544 --> 02:22:19,149 BECAUSE MANY HAVE POSITIVE HIV 2705 02:22:19,149 --> 02:22:21,886 SPECIFIC CELLS THE SECOND IS THE 2706 02:22:21,886 --> 02:22:23,454 REGULATORY ASPECT OF PEDIATRIC 2707 02:22:23,454 --> 02:22:24,488 CARE AND WE HAVE TO RESPECT THAT 2708 02:22:24,488 --> 02:22:29,994 AND DO WHAT WE FEEL IS GOING TO 2709 02:22:29,994 --> 02:22:36,834 BE SAFE WITH EFFECTS AND HAVING 2710 02:22:36,834 --> 02:22:38,435 AN APPROACH TO PEDIATRIC STUDIES 2711 02:22:38,435 --> 02:22:43,007 WITH A FOCUS ON DIFFERENT 2712 02:22:43,007 --> 02:22:44,708 CONSIDERATIONS THE AIDS SPECTRUM 2713 02:22:44,708 --> 02:22:49,713 IS GOING TO BE CRITICAL 2714 02:22:49,713 --> 02:22:50,080 EFFICIENT. 2715 02:22:50,080 --> 02:22:53,784 AND THERE'S RESTRICTED FUNDING 2716 02:22:53,784 --> 02:22:58,355 SO THERE'S PRIORITIZATION AND 2717 02:22:58,355 --> 02:22:59,590 PROOF OF CONCEPT STUDIES MAY NOT 2718 02:22:59,590 --> 02:23:00,624 BE THE TOP PRIORITY. 2719 02:23:00,624 --> 02:23:03,961 AND THE ETHICAL CONSIDERATIONS 2720 02:23:03,961 --> 02:23:07,431 FOR CONSENT AND ASCENT. 2721 02:23:07,431 --> 02:23:10,234 MANY HURDLES BUT I THINK WE'RE 2722 02:23:10,234 --> 02:23:12,303 IN A UNIQUE POSITION BASED ON 2723 02:23:12,303 --> 02:23:14,939 THE DIFFERENCES IN PEDIATRIC 2724 02:23:14,939 --> 02:23:16,240 RESERVOIRS TO ACHIEVE REMISSION 2725 02:23:16,240 --> 02:23:22,479 AND CURE FOR THIS POPULATION. 2726 02:23:22,479 --> 02:23:25,582 I'LL TOUCH ON THE FINDING 2727 02:23:25,582 --> 02:23:27,384 MAURICIO PRESENTED YESTERDAY AND 2728 02:23:27,384 --> 02:23:28,018 WE'RE LEARNING A LOT ON THE 2729 02:23:28,018 --> 02:23:33,190 PROFESSION I THINK WILL HELP. 2730 02:23:33,190 --> 02:23:35,859 HOW DO YOU MOVE THE INFANT STUDY 2731 02:23:35,859 --> 02:23:38,362 IN A MACAQUE MODEL TO CHILDREN 2732 02:23:38,362 --> 02:23:39,430 AND AT WHAT AGE SHOULD WE START 2733 02:23:39,430 --> 02:23:47,438 AND HOW DO WE TRANSLATE STUDIES 2734 02:23:47,438 --> 02:23:51,842 FROM A TWO-WEEK-OLD INFANT TO A 2735 02:23:51,842 --> 02:23:55,479 2-YEAR-OLD CHILD. 2736 02:23:55,479 --> 02:24:02,753 THERE'S INVESTMENT IN THE AGENDA 2737 02:24:02,753 --> 02:24:04,388 AND THEY MOVED THIS PRECLINICAL 2738 02:24:04,388 --> 02:24:10,427 STUDY TO CLINICAL TRIALS. 2739 02:24:10,427 --> 02:24:11,895 THE SAME PEOPLE DOING THE TRIALS 2740 02:24:11,895 --> 02:24:17,201 ARE DEVELOPING THE PROTOCOL AND 2741 02:24:17,201 --> 02:24:26,043 CONCEPT AND IT'S TIME CONSUMING 2742 02:24:26,043 --> 02:24:27,745 AND GET WITH THE FDA TO BEGIN TO 2743 02:24:27,745 --> 02:24:33,550 SEE HOW TO MOVE THE JUNE 2744 02:24:33,550 --> 02:24:39,757 DELIVERY SYSTEM OF BIOLOGICS IS 2745 02:24:39,757 --> 02:24:41,825 PROMISING AND PROCUREMENT OF 2746 02:24:41,825 --> 02:24:42,059 PRODUCT. 2747 02:24:42,059 --> 02:24:46,196 THEY'VE BEEN ABLE TO HELP US 2748 02:24:46,196 --> 02:24:47,564 CONNECT AND CONTACT VARIOUS 2749 02:24:47,564 --> 02:24:48,766 ORGANIZATIONS THINKING ABOUT 2750 02:24:48,766 --> 02:24:53,237 PRODUCT DEVELOPMENT. 2751 02:24:53,237 --> 02:24:56,840 LASTLY AND WHATEVER WE FIND HAS 2752 02:24:56,840 --> 02:24:58,709 TO BE ABLE TO IMPLEMENT THIS. 2753 02:24:58,709 --> 02:25:00,544 IT'S NOT JUST CLINICAL TRIALS 2754 02:25:00,544 --> 02:25:01,211 AND ENGAGING IN COMMUNITY THEY 2755 02:25:01,211 --> 02:25:03,113 WANT TO KNOW IF WE FIND 2756 02:25:03,113 --> 02:25:06,717 SOMETHING WE HAVE A PLAN TO MOVE 2757 02:25:06,717 --> 02:25:07,885 THIS OUT ON A LARGER SCALE. 2758 02:25:07,885 --> 02:25:11,455 WITH THAT I'LL STOP AND TURN IT 2759 02:25:11,455 --> 02:25:19,096 OVER TO DAVE. 2760 02:25:19,096 --> 02:25:23,067 WE'RE ALL THINKING OF THE SAME 2761 02:25:23,067 --> 02:25:28,906 THING AND I'LL TRY TO ADD 2762 02:25:28,906 --> 02:25:33,143 SOMETHING DIFFERENT. 2763 02:25:33,143 --> 02:25:34,978 IT MY BE WORTHWHILE TO REFLECT 2764 02:25:34,978 --> 02:25:37,448 BACK ON AN OPINION PIECE WRITTEN 2765 02:25:37,448 --> 02:25:38,449 IN SCIENCE AT THE BEGINNING OF 2766 02:25:38,449 --> 02:25:48,759 THE COLLABORATORY. 2767 02:25:52,963 --> 02:25:55,632 AND EFFORT HAS BEEN USEFUL AND 2768 02:25:55,632 --> 02:25:56,233 SUCCESSFUL OVER NOW ALMOST 20 2769 02:25:56,233 --> 02:26:05,976 YEARS. 2770 02:26:05,976 --> 02:26:09,913 THERE'S DIFFERENT NEEDS AND THE 2771 02:26:09,913 --> 02:26:13,750 QUESTION IS WHETHER THE CURRENT 2772 02:26:13,750 --> 02:26:19,423 FUNDING IN IMPLEMENTING SYSTEMS 2773 02:26:19,423 --> 02:26:21,291 ARE THERE'S SEVERAL ONES TO PUSH 2774 02:26:21,291 --> 02:26:22,526 DIFFERENT THINGS FORWARD OR 2775 02:26:22,526 --> 02:26:26,897 WHETHER WE NEED SOME A NEW NOVEL 2776 02:26:26,897 --> 02:26:32,236 DIFFERENT OR SPECIAL STRUCTURE 2777 02:26:32,236 --> 02:26:38,308 TO DO THAT RECOGNIZING THE 2778 02:26:38,308 --> 02:26:43,247 INFRASTRUCTURE HAS MULTIPLE 2779 02:26:43,247 --> 02:26:45,449 OTHER DEMANDS AND DEMANDS ON 2780 02:26:45,449 --> 02:26:51,054 SCIENCE AND MEDICINE WE'LL BE 2781 02:26:51,054 --> 02:26:55,592 FINDING ABOUT SOON. 2782 02:26:55,592 --> 02:26:59,463 ON WHAT KINDS OF IDEAS CAN BE 2783 02:26:59,463 --> 02:27:02,099 MORE RAPIDLY BROUGHT OUT OF STFB 2784 02:27:02,099 --> 02:27:04,635 AREA OF WHICH THIS GROUP IS -- 2785 02:27:04,635 --> 02:27:05,636 SCIENTIFIC GROUP WHERE THIS 2786 02:27:05,636 --> 02:27:07,004 GROUP IS A FERTILE FIELD AND HOW 2787 02:27:07,004 --> 02:27:13,343 THAT CAN BE BROUGHT FORWARD FOR 2788 02:27:13,343 --> 02:27:19,917 DIFFERENT APPROACHES AND TRIALS. 2789 02:27:19,917 --> 02:27:23,353 I AGREE THE STICKING POINT IS 2790 02:27:23,353 --> 02:27:27,758 FROM ANIMAL MODEL TO PEOPLE AND 2791 02:27:27,758 --> 02:27:28,625 HAVING RESOURCE OR FUNDS OR 2792 02:27:28,625 --> 02:27:29,526 SUPPORT TO PRODUCE IT'S PROBABLY 2793 02:27:29,526 --> 02:27:32,329 NOT A PRODUCT. 2794 02:27:32,329 --> 02:27:40,571 I THINK IT'S A TOOL OR CANDIDATE 2795 02:27:40,571 --> 02:27:46,109 MOLECULE OR SOME EXPERIMENTAL 2796 02:27:46,109 --> 02:27:49,746 COMPOUND THAT WOULD BE CAN BE A 2797 02:27:49,746 --> 02:27:52,449 MOLECULE AND ALREADY BEING MADE 2798 02:27:52,449 --> 02:27:57,654 IN THE VACCINE AND PREVENTION 2799 02:27:57,654 --> 02:28:01,525 SPHERE WHETHER THERE NEEDS TO BE 2800 02:28:01,525 --> 02:28:04,061 MORE USE OF THOSE RESOURCE OR 2801 02:28:04,061 --> 02:28:07,431 CONSTRUCTION OF A NEW 2802 02:28:07,431 --> 02:28:11,001 INFRASTRUCTURE TO PRODUCE 2803 02:28:11,001 --> 02:28:12,569 SMALLER NOVEL PNEUMOTHERAPIES 2804 02:28:12,569 --> 02:28:13,136 BUT IT'S SOMETHING TO THINK 2805 02:28:13,136 --> 02:28:20,577 ABOUT. 2806 02:28:20,577 --> 02:28:25,749 AS I RECALL THERE WAS A DEEP 2807 02:28:25,749 --> 02:28:28,986 INVESTMENT WE WERE HOPING THAT 2808 02:28:28,986 --> 02:28:31,655 WOULD DO THE WORK TRANSFERRING 2809 02:28:31,655 --> 02:28:36,126 FROM LAB TO CLINIC. 2810 02:28:36,126 --> 02:28:43,000 ON ZOOM WE HAVE ANDY CATES TO 2811 02:28:43,000 --> 02:28:46,169 GIVE US THE -- ANDY KAYTES AND 2812 02:28:46,169 --> 02:28:49,773 I'LL LET KATIE GO NEXT AND THEN 2813 02:28:49,773 --> 02:28:49,973 ANDY. 2814 02:28:49,973 --> 02:28:59,016 KATIE. 2815 02:28:59,016 --> 02:29:04,121 YOU'RE STILL ON MUTE. 2816 02:29:04,121 --> 02:29:10,661 SIGN LANGUAGE? 2817 02:29:10,661 --> 02:29:13,764 >> I WAS TRYING TO UNMUTE. 2818 02:29:13,764 --> 02:29:17,567 SORRY. 2819 02:29:17,567 --> 02:29:19,736 CAN YOU HEAR ME NOW? 2820 02:29:19,736 --> 02:29:21,204 I'M A TRANSLATIONAL RESEARCHER 2821 02:29:21,204 --> 02:29:22,906 AT THE UNIVERSITY OF 2822 02:29:22,906 --> 02:29:24,274 PENNSYLVANIA. 2823 02:29:24,274 --> 02:29:27,010 I'VE BEEN HER VICE CHAIR IN THE 2824 02:29:27,010 --> 02:29:32,115 ACTG CURE TSG THE PAST THREE 2825 02:29:32,115 --> 02:29:32,649 YEARS. 2826 02:29:32,649 --> 02:29:33,717 THOUGH I'VE BEEN GRABBING HER 2827 02:29:33,717 --> 02:29:36,219 WITH MY NAILS AND NOT LETTING 2828 02:29:36,219 --> 02:29:37,954 HER GO SHE'S ALLOWED TO MOVE ON 2829 02:29:37,954 --> 02:29:41,758 AND IN 10 DAYS MYSELF AND 2830 02:29:41,758 --> 02:29:45,395 JONATHAN LEE WILL BE LEADING THE 2831 02:29:45,395 --> 02:29:45,662 GROUP. 2832 02:29:45,662 --> 02:29:47,264 THREES A SMALL MECHANISM THROUGH 2833 02:29:47,264 --> 02:29:54,137 THE ATCG SEVERAL CONCEPTS MOVED 2834 02:29:54,137 --> 02:29:54,638 FORWARD THROUGH. 2835 02:29:54,638 --> 02:30:00,610 THAT'S ONE PATHWAY FOR IDEAS 2836 02:30:00,610 --> 02:30:05,582 GENERATED THROUGH THE A STRONG 2837 02:30:05,582 --> 02:30:10,954 PATHWAY IN THAT REGARD. 2838 02:30:10,954 --> 02:30:13,290 I'LL ECHO THE CONCERNS ABOUT THE 2839 02:30:13,290 --> 02:30:18,695 NEED FOR STRONG INDUSTRY 2840 02:30:18,695 --> 02:30:20,397 PARTNERSHIPS WHETHER WITH AN NIH 2841 02:30:20,397 --> 02:30:30,841 BODY OR INDUSTRY PARTNER. 2842 02:30:32,242 --> 02:30:35,078 THAT'S HOW WE ME OF FORWARD 2843 02:30:35,078 --> 02:30:36,780 AROUND RECOGNIZING WE'RE AN 2844 02:30:36,780 --> 02:30:40,217 EXPERIMENTAL MEDICINE STUDIES 2845 02:30:40,217 --> 02:30:41,618 AND ASKING THE RIGHT SCIENTIFIC 2846 02:30:41,618 --> 02:30:44,187 QUESTIONS WITH AMPLE SAMPLES AND 2847 02:30:44,187 --> 02:30:46,456 TIMING AND REGIMENTS AND WHAT 2848 02:30:46,456 --> 02:30:50,227 NOT WITH FEASIBILITY IS A HUGE 2849 02:30:50,227 --> 02:30:55,365 CHALLENGE FOR THESE STUDIES AT 2850 02:30:55,365 --> 02:30:57,234 THIS POINT. 2851 02:30:57,234 --> 02:31:00,437 IT BECOMES A LOGISTICAL OR 2852 02:31:00,437 --> 02:31:02,472 PRACTICAL ISSUE THINKING OF THE 2853 02:31:02,472 --> 02:31:07,644 PEDIATRIC PARALLELS TO ADULT AND 2854 02:31:07,644 --> 02:31:10,914 PEDIATRIC STUDIES. 2855 02:31:10,914 --> 02:31:12,249 WE'RE FAR BEHIND IN 2856 02:31:12,249 --> 02:31:13,083 UNDERSTANDING THESE IN WOMEN 2857 02:31:13,083 --> 02:31:17,087 COMPARED TO MEN AND IT MAY BE 2858 02:31:17,087 --> 02:31:19,122 BECAUSE OF HOW INFEASIBLE OUR 2859 02:31:19,122 --> 02:31:19,723 STUDY ARE. 2860 02:31:19,723 --> 02:31:22,659 THE MORE REASONABLE WE MAKE THE 2861 02:31:22,659 --> 02:31:27,664 STUDIES FOR PARTICIPANTS, THE 2862 02:31:27,664 --> 02:31:37,874 MORE ABLE WE ARE TO TRULY ENROLL 2863 02:31:37,874 --> 02:31:40,177 FOR THOSE W.H.O. CRAN KNOT PRART 2864 02:31:40,177 --> 02:31:40,844 OPERATE FOR A LONG PERIOD OF 2865 02:31:40,844 --> 02:31:41,845 TIME IN THE STUDIES. 2866 02:31:41,845 --> 02:31:44,047 WITH THAT I DON'T THINK I'VE 2867 02:31:44,047 --> 02:31:49,486 RAISED PARTICULARLY NEW CONCEPTS 2868 02:31:49,486 --> 02:31:55,792 BUT I DO THINK THIS WILL HELP US 2869 02:31:55,792 --> 02:31:59,696 MOVE THE FIELD FORWARD. 2870 02:31:59,696 --> 02:32:05,035 THANK YOU. 2871 02:32:05,035 --> 02:32:06,002 >> ANDY. 2872 02:32:06,002 --> 02:32:06,937 >> THANK YOU VERY MUCH. 2873 02:32:06,937 --> 02:32:11,508 I AGREE WITH EVERYTHING THAT'S 2874 02:32:11,508 --> 02:32:13,777 BEEN SAID I'M FROM THE 2875 02:32:13,777 --> 02:32:15,579 UNIVERSITY OF CALIFORNIA SUNDAY 2876 02:32:15,579 --> 02:32:18,515 AND I'M PRART OF THE HIV 2877 02:32:18,515 --> 02:32:18,982 COLLABORATORY. 2878 02:32:18,982 --> 02:32:20,283 I'VE BEEN FORTUNATE ENOUGH TO BE 2879 02:32:20,283 --> 02:32:22,919 INVOLVED IN THE MDC SINCE THE 2880 02:32:22,919 --> 02:32:27,657 FIRST ITERATION. 2881 02:32:27,657 --> 02:32:30,827 I'M FORTUNATE TO BE PART OF THE 2882 02:32:30,827 --> 02:32:34,498 CURE TSG WITH WONDERFUL 2883 02:32:34,498 --> 02:32:39,870 LEADERSHIP WITH MA MARINA AND 2884 02:32:39,870 --> 02:32:41,438 KATIE. 2885 02:32:41,438 --> 02:32:42,839 IT'S BEEN WONDERFUL. 2886 02:32:42,839 --> 02:32:47,944 FROM A COMMUNITY STANDPOINT I 2887 02:32:47,944 --> 02:32:51,882 THINK WE'RE STARING INTO A 2888 02:32:51,882 --> 02:32:57,654 CRYSTAL BALL AND HOPING FOR AN 2889 02:32:57,654 --> 02:33:01,558 IMAGE WHAT HIV WILL BE LIKE IN 2890 02:33:01,558 --> 02:33:10,000 THE COMMUNITY. 2891 02:33:10,000 --> 02:33:12,802 WE HAVE CONCERN ABOUT 2892 02:33:12,802 --> 02:33:14,371 SCALABILITY AND WILL IT BE 2893 02:33:14,371 --> 02:33:20,143 AVAILABLE FOR ALL AND IS A CURE 2894 02:33:20,143 --> 02:33:27,450 GOING TO BE AS AVAILABLE IN THE 2895 02:33:27,450 --> 02:33:30,353 DEEPEST PART OF AFRICA AS WELL 2896 02:33:30,353 --> 02:33:31,421 AS NEW YORK CITY? 2897 02:33:31,421 --> 02:33:34,090 IMPORTANT TO THE COMMUNITY IS WE 2898 02:33:34,090 --> 02:33:39,863 ARE UNABLE TO TRANSMIT TO A 2899 02:33:39,863 --> 02:33:41,631 PARTNER THAT IS WE AND PEOPLE 2900 02:33:41,631 --> 02:33:47,437 WOULD LIKE TO BE ABLE TO HAVE AN 2901 02:33:47,437 --> 02:33:53,343 HIV NEGATIVE TEST ON AN EXAMPLE 2902 02:33:53,343 --> 02:33:57,547 BUT THAT SAID THERE'S THE ISSUE 2903 02:33:57,547 --> 02:33:59,983 OF BECOMING HIV NEGATIVE AFTER 2904 02:33:59,983 --> 02:34:03,420 LIVING WITH HIV AFTER HOWEVER, 2905 02:34:03,420 --> 02:34:11,428 LONG, NOW YOUR ALL OF A SUDDEN 2906 02:34:11,428 --> 02:34:13,163 OF THE RYAN WHITE SYSTEMS BUILT 2907 02:34:13,163 --> 02:34:14,598 FOR HIV. 2908 02:34:14,598 --> 02:34:17,434 THOSE ARE THINGS THAT KIND OF 2909 02:34:17,434 --> 02:34:19,436 COME INTO PLAY AND WHEN YOU TALK 2910 02:34:19,436 --> 02:34:29,112 ABOUT GETTING INTO THE CLINIC A 2911 02:34:29,112 --> 02:34:33,016 THOUGHT COMES TO MIND OF A CAR T 2912 02:34:33,016 --> 02:34:34,517 CELL TRIAL AT CITY OF HOPE AND 2913 02:34:34,517 --> 02:34:37,053 YOU NEED TO STAY AT THE CITY OF 2914 02:34:37,053 --> 02:34:39,289 HOPE FOR TO WEEKS STRAIGHT AS A 2915 02:34:39,289 --> 02:34:39,589 PARTICIPANT. 2916 02:34:39,589 --> 02:34:40,757 SO IS THAT THE KIND OF THING 2917 02:34:40,757 --> 02:34:42,626 THAT IS GOING TO BE NECESSARY 2918 02:34:42,626 --> 02:34:45,662 FOR SOMEONE TO RECEIVE A CURE OR 2919 02:34:45,662 --> 02:34:51,334 AS SIMPLE AS TAKING AN ASPIRIN? 2920 02:34:51,334 --> 02:34:55,071 I THINK HOPEFULLY THE TRUTH IS 2921 02:34:55,071 --> 02:34:55,572 IN THE MIDDLE. 2922 02:34:55,572 --> 02:34:56,272 CLOSER TO THE ASPIRIN WOULD BE 2923 02:34:56,272 --> 02:35:06,383 NICE. 2924 02:35:08,251 --> 02:35:10,654 WE TALK ABOUT DIFFERENT GENETICS 2925 02:35:10,654 --> 02:35:11,588 FOR PERSON OR BIO TYPE AND HOW 2926 02:35:11,588 --> 02:35:20,497 IS THAT GOING TO WORK? 2927 02:35:20,497 --> 02:35:24,034 CAN THAT BE DONE IN A SIMPLE WAY 2928 02:35:24,034 --> 02:35:25,235 OR BE A LARGER TWEAK TO GET 2929 02:35:25,235 --> 02:35:27,504 SOMETHING TO FIT INTO A CERTAIN 2930 02:35:27,504 --> 02:35:37,747 PERSON'S BODY? 2931 02:35:42,519 --> 02:35:43,820 WE HAVE THE DAMAGE OF THE 2932 02:35:43,820 --> 02:35:44,721 MEDICATIONS OVER THE YEARS 2933 02:35:44,721 --> 02:35:46,756 PEOPLE HAVE TAKEN. 2934 02:35:46,756 --> 02:35:49,826 CERTAINLY IT'S NOT GOING TO BE 2935 02:35:49,826 --> 02:35:51,628 AS MUCH OF AN ISSUE OF THOSE 2936 02:35:51,628 --> 02:35:56,833 TREATED WITH ART. 2937 02:35:56,833 --> 02:35:59,436 FOR A NUMBER OF PEOPLE MAJORITY 2938 02:35:59,436 --> 02:36:01,371 OF PEOPLE OVER 50 RIGHT NOW 2939 02:36:01,371 --> 02:36:03,206 THAT'S A REAL SITUATION. 2940 02:36:03,206 --> 02:36:07,811 SO WILL THINGS LIKE NEUROPATHY, 2941 02:36:07,811 --> 02:36:08,845 COGNITION, OTHER INFLAMMATORY 2942 02:36:08,845 --> 02:36:11,548 ISSUES BE ABLE TO BE REVERSED 2943 02:36:11,548 --> 02:36:12,615 AND PUT BACK TO WHAT THEY ARE 2944 02:36:12,615 --> 02:36:16,686 WERE PRIOR TO US TAKING ART? 2945 02:36:16,686 --> 02:36:22,425 DON'T KNOW THAT'S REALLY GOING 2946 02:36:22,425 --> 02:36:26,629 TO BE SOMETHING WE'RE ABLE TO 2947 02:36:26,629 --> 02:36:31,434 ACCOMPLISH FOR NOT. 2948 02:36:31,434 --> 02:36:32,602 IT'S REALLY DIFFICULT TO 2949 02:36:32,602 --> 02:36:34,104 FORECAST WHAT A CURE WILL LOOK 2950 02:36:34,104 --> 02:36:38,041 LIKE INSIDE THE CLINIC BUT IT'S 2951 02:36:38,041 --> 02:36:40,143 GOING TO TAKE PHARMACEUTICAL 2952 02:36:40,143 --> 02:36:41,511 COMPANIES PLAYING WELL WITH ONE 2953 02:36:41,511 --> 02:36:41,745 ANOTHER. 2954 02:36:41,745 --> 02:36:43,646 I ASSUME WE WON'T BE WORKING 2955 02:36:43,646 --> 02:36:44,481 WITH ONE COMPOUND. 2956 02:36:44,481 --> 02:36:47,317 IT WILL IB ACOMBINATION THERAPY 2957 02:36:47,317 --> 02:36:47,917 OF SORTS. 2958 02:36:47,917 --> 02:36:50,220 WILL THE BE REPEATED THERAPIES 2959 02:36:50,220 --> 02:36:52,822 OVER THE COURSE OF WEEKS, 2960 02:36:52,822 --> 02:36:53,890 MONTHS, YEARS. 2961 02:36:53,890 --> 02:36:55,158 WHAT HAPPENS AS FAR AS THE 2962 02:36:55,158 --> 02:36:59,295 TESTING TO FIND OUT IF SOMEBODY 2963 02:36:59,295 --> 02:37:01,030 ACTUALLY IS HIV NEGATIVE AND 2964 02:37:01,030 --> 02:37:03,533 CURED AND DOESN'T NEED TO BE ON 2965 02:37:03,533 --> 02:37:06,002 ART ANYMORE? 2966 02:37:06,002 --> 02:37:08,972 HOW WOULD THIS PLAY IN THE 2967 02:37:08,972 --> 02:37:10,540 INCARCERATED POPULATIONS. 2968 02:37:10,540 --> 02:37:17,614 LOTS OF QUESTIONS TO ANSWER. 2969 02:37:17,614 --> 02:37:19,015 AND I THE COMMUNITY IS FULL OF 2970 02:37:19,015 --> 02:37:29,592 QUESTIONS MORE THAN ANSWERS. 2971 02:37:29,592 --> 02:37:31,427 >> WHY DON'T WE TRY TO COME UP 2972 02:37:31,427 --> 02:37:32,962 WITH SOLUTIONS. 2973 02:37:32,962 --> 02:37:35,098 WE OUTLINED THE PROBLEMS AND 2974 02:37:35,098 --> 02:37:40,136 BARRIERS AND THEY'RE CONSISTENT. 2975 02:37:40,136 --> 02:37:50,680 LET'S FOR EXAMPLE, THINK ABOUT 2976 02:37:52,215 --> 02:37:56,486 AND THERE'S BEEN WORK ON USING 2977 02:37:56,486 --> 02:37:58,054 SOME CUTTING EDGE GENE EDITING 2978 02:37:58,054 --> 02:38:03,693 TOOL TO DIRECTLY ACTIVATING THE 2979 02:38:03,693 --> 02:38:13,937 HIV PROVIRUS. 2980 02:38:16,139 --> 02:38:17,473 AND INFECT WITH HIV RATHER THAN 2981 02:38:17,473 --> 02:38:21,578 DEPENDING ON THE PROD ACTIVATING 2982 02:38:21,578 --> 02:38:21,878 APPROACHES. 2983 02:38:21,878 --> 02:38:23,012 THESE ARE PRODUCTS THAT ARE 2984 02:38:23,012 --> 02:38:25,014 GOING TO HAVE TO GO THROUGH THE 2985 02:38:25,014 --> 02:38:25,682 PRECLINICAL DEVELOPMENT. 2986 02:38:25,682 --> 02:38:28,184 SOMEONE WILL HAVE TO DO ALL THE 2987 02:38:28,184 --> 02:38:28,551 TALK STUFF. 2988 02:38:28,551 --> 02:38:30,520 MAKE A PRODUCT. 2989 02:38:30,520 --> 02:38:32,755 ALL THE RELEASE CRITERIA. 2990 02:38:32,755 --> 02:38:35,191 THAT'S USUALLY A TWO, FOUR, 2991 02:38:35,191 --> 02:38:45,735 MILLION DOLLAR KIND OF THING AND 2992 02:38:46,803 --> 02:38:49,339 SMAC MIMETICS. 2993 02:38:49,339 --> 02:38:50,707 WE NEED ALL THIS STUFF TO BE 2994 02:38:50,707 --> 02:38:51,274 PRODUCED. 2995 02:38:51,274 --> 02:38:56,512 WHAT MODELS DO WE NEED TO FUND 2996 02:38:56,512 --> 02:39:06,990 THAT AND INVESTMENT FOR THE 2997 02:39:09,092 --> 02:39:09,993 PRODUCTS. 2998 02:39:09,993 --> 02:39:10,793 WE SHOULD LOOK TO THE VACCINE 2999 02:39:10,793 --> 02:39:15,632 EFFORTS IN WHICH THE 3000 02:39:15,632 --> 02:39:16,332 COLLABORATORIES THEY ARE HAVE 3001 02:39:16,332 --> 02:39:17,400 THE THEY ARE HAVE THE CAPACITY 3002 02:39:17,400 --> 02:39:21,537 TO DO BASIC DISCOVERY AND HAVE 3003 02:39:21,537 --> 02:39:28,077 CAPACITY WORKING WITH GNP 3004 02:39:28,077 --> 02:39:33,316 FACILITIES TO MAKE THE PRODUCTS. 3005 02:39:33,316 --> 02:39:34,250 THEY'RE MUCH BIGGER. 3006 02:39:34,250 --> 02:39:35,752 THEY HAVE THIS CAPACITY TO MAKE 3007 02:39:35,752 --> 02:39:41,357 THE PRODUCTS AND THEN THERE'S 3008 02:39:41,357 --> 02:39:50,133 IDEAS FORMED IN THE LABS THE 3009 02:39:50,133 --> 02:39:53,436 GERM LINE STUFF AND TRANSITION 3010 02:39:53,436 --> 02:39:54,370 TO THE NETWORK. 3011 02:39:54,370 --> 02:39:56,472 SAMPLES COME BACK AND SO FORTH. 3012 02:39:56,472 --> 02:39:58,441 WE DON'T HAVE THE CAPACITY. 3013 02:39:58,441 --> 02:39:59,876 SHOULD BE? 3014 02:39:59,876 --> 02:40:04,147 SHOULD THE COLLABORATORIES TO 3015 02:40:04,147 --> 02:40:05,581 HAVE THE CAPACITY AND WHO WILL 3016 02:40:05,581 --> 02:40:07,016 DO THE WORK? 3017 02:40:07,016 --> 02:40:08,985 JUST THROWING THAT OUT THERE. 3018 02:40:08,985 --> 02:40:11,120 IF OTHER PEOPLE HAVE POTENTIAL 3019 02:40:11,120 --> 02:40:13,823 SOLUTIONS FEEL FREE. 3020 02:40:13,823 --> 02:40:18,728 SANDY AND THEN DAVID. 3021 02:40:18,728 --> 02:40:19,829 >> I APPRECIATE THE 3022 02:40:19,829 --> 02:40:21,497 SOLUTION-BASED APPROACH AND 3023 02:40:21,497 --> 02:40:23,299 REFLECTING ON ANDY'S ELOQUENT 3024 02:40:23,299 --> 02:40:25,001 COMMENTS WE'RE TRYING TO 3025 02:40:25,001 --> 02:40:26,402 OVERCOME TWO SETS OF HURDLES 3026 02:40:26,402 --> 02:40:29,472 WHEN WE TALK ABOUT TRANSLATING 3027 02:40:29,472 --> 02:40:29,872 STRATEGIES. 3028 02:40:29,872 --> 02:40:31,541 THE FIRST IS THAT EARLY 3029 02:40:31,541 --> 02:40:32,942 TRANSLATION GETTING SOME OF 3030 02:40:32,942 --> 02:40:38,648 THESE IDEAS COMING OUT OF THE 3031 02:40:38,648 --> 02:40:43,586 MDCs INTO PEOPLE. 3032 02:40:43,586 --> 02:40:45,088 AND GETTING THEM TO A SMALL SET 3033 02:40:45,088 --> 02:40:46,422 OF PEOPLE AND PROOF OF CONCEPT 3034 02:40:46,422 --> 02:40:48,791 IS ONE BIG HURDLE AND TAKING 3035 02:40:48,791 --> 02:40:50,660 THAT FURTHER, I MEAN WE HAVE 3036 02:40:50,660 --> 02:40:52,962 CURED PEOPLE AS A FIELD BUT 3037 02:40:52,962 --> 02:40:55,131 THROUGH STEM CELL 3038 02:40:55,131 --> 02:40:55,498 TRANSPLANTATION. 3039 02:40:55,498 --> 02:41:02,271 OR BONE MARROW TRANSPLANTATION 3040 02:41:02,271 --> 02:41:07,243 IT'S CREATED HOPE IT'S POSSIBLE. 3041 02:41:07,243 --> 02:41:09,645 WE HAVE TO THINK OF THOSE 3042 02:41:09,645 --> 02:41:12,081 OVERLAPPING AND DIFFERENT 3043 02:41:12,081 --> 02:41:15,885 BUCKETS OF EARLY TRANSLATION AND 3044 02:41:15,885 --> 02:41:16,886 SCALABILITY. 3045 02:41:16,886 --> 02:41:19,122 AND FOR SOLUTION I APPRECIATE 3046 02:41:19,122 --> 02:41:25,928 YOUR ANALOGY THE VACCINE REALM 3047 02:41:25,928 --> 02:41:33,903 WE WORK UNBOTH -- IN BOTH 3048 02:41:33,903 --> 02:41:39,042 PLACES AND THERE'S GRANTS FOR 3049 02:41:39,042 --> 02:41:43,813 ADDRESSING THESE ISSUES. 3050 02:41:43,813 --> 02:41:46,416 THEY COULD BE A SUPPLEMENT TO 3051 02:41:46,416 --> 02:41:48,017 THE MDCs IF YOU MEET CERTAIN 3052 02:41:48,017 --> 02:41:51,587 CRITERIA YOU CAN APPLY FOR A 3053 02:41:51,587 --> 02:41:53,156 SUPPLEMENT TO GET INTO THE MORE 3054 02:41:53,156 --> 02:41:55,425 RESOURCE INTENSIVE CLINICAL 3055 02:41:55,425 --> 02:42:02,965 DEVELOPMENT PHASE. 3056 02:42:02,965 --> 02:42:06,869 >> STIMULATED BY WHAT YOU SAID. 3057 02:42:06,869 --> 02:42:09,038 PHARMA COMPANIES ARE EN BUSINESS 3058 02:42:09,038 --> 02:42:10,540 TO STAY IN BUSINESS MAKING 3059 02:42:10,540 --> 02:42:12,975 MEDICINES FOR PEOPLE. 3060 02:42:12,975 --> 02:42:14,944 THEY HAVE TO SELL THEM AND STAY 3061 02:42:14,944 --> 02:42:17,847 IN BUSINESS. 3062 02:42:17,847 --> 02:42:20,183 THEY'RE UNDER VARIOUS PRESSURES 3063 02:42:20,183 --> 02:42:23,653 DIFFERENT THAN SOME OTHER PEOPLE 3064 02:42:23,653 --> 02:42:31,427 IN THE ROOM. 3065 02:42:31,427 --> 02:42:38,434 WE COULD ASK THE NIH TO MAKE A 3066 02:42:38,434 --> 02:42:41,003 MOLECULE. 3067 02:42:41,003 --> 02:42:42,038 AND MAYBE NOT TO BE DISCUSSED 3068 02:42:42,038 --> 02:42:44,674 ONLINE WITH A ZILLION PEOPLE BUT 3069 02:42:44,674 --> 02:42:49,645 FURTHER CONVERSATIONS TO 3070 02:42:49,645 --> 02:42:51,747 APPROACH THE RELEVANT FAR PLA 3071 02:42:51,747 --> 02:42:53,850 INTEREST AND SEE IF THERE'S 3072 02:42:53,850 --> 02:42:55,685 SOMETHING IN THE MIDDLE. 3073 02:42:55,685 --> 02:42:59,555 COULD WE CONTRACTOR AGREE WITH 3074 02:42:59,555 --> 02:43:01,357 SOME OF THEM TO COLLABORATE TO 3075 02:43:01,357 --> 02:43:05,161 PROVIDE SOME OF THE SERVICES AT 3076 02:43:05,161 --> 02:43:08,197 SOME TIME WITH SOME SORT OF SKIN 3077 02:43:08,197 --> 02:43:09,899 IN THE GAME ON BOTH SIDES AND 3078 02:43:09,899 --> 02:43:11,200 BENEFIT ON BOTH SIDES. 3079 02:43:11,200 --> 02:43:13,870 IT WOULD BE A NOVEL WAY TO 3080 02:43:13,870 --> 02:43:17,006 APPROACH IT. 3081 02:43:17,006 --> 02:43:18,074 MAY BE THE NEXT PANEL CAN 3082 02:43:18,074 --> 02:43:19,375 DISCUSS THEIR OBSTACLES AND WHAT 3083 02:43:19,375 --> 02:43:21,410 THEY THINK ABOUT THAT AND IF 3084 02:43:21,410 --> 02:43:22,645 THEY HAVE SOME OTHER PARALLEL 3085 02:43:22,645 --> 02:43:32,922 SORTS OF IDEAS. 3086 02:43:33,589 --> 02:43:35,558 THE OTHER TRIGGER POINT IS THE 3087 02:43:35,558 --> 02:43:38,728 DECISION ABOUT WHO OR WHEN IT 3088 02:43:38,728 --> 02:43:40,997 GETS TO BE DECIDED SOME APPROACH 3089 02:43:40,997 --> 02:43:44,000 OR SOME MOLECULE IS WORTH THIS 3090 02:43:44,000 --> 02:43:48,671 INVESTMENT TO GO FORWARD INTO 3091 02:43:48,671 --> 02:43:53,476 HUMAN STUDIES. 3092 02:43:53,476 --> 02:43:57,480 THE DECISION MADE BY A PROGRAM 3093 02:43:57,480 --> 02:44:06,589 OR FEDERAL ENTITY. 3094 02:44:06,589 --> 02:44:13,863 OR PEOPLE LIKE THE GATES AND A 3095 02:44:13,863 --> 02:44:23,940 PARALLEL PRAC. 3096 02:44:23,940 --> 02:44:26,375 THERE'S BEEN A PROCESS AND THOSE 3097 02:44:26,375 --> 02:44:30,213 ARE OTHER PLAYERS OUT THERE THAT 3098 02:44:30,213 --> 02:44:32,315 MIGHT BE WILLING TO JOIN TO MAKE 3099 02:44:32,315 --> 02:44:35,418 THAT INVESTMENTS TO MOVE 3100 02:44:35,418 --> 02:44:45,561 FORWARD. 3101 02:44:49,765 --> 02:44:51,100 >> HAVING ONGOING CONVERSATIONS 3102 02:44:51,100 --> 02:44:53,135 WITH THE PROGRAM OFFICERS AND 3103 02:44:53,135 --> 02:44:54,971 THE CLINICAL TRIALS NETWORK WAS 3104 02:44:54,971 --> 02:45:00,243 HELPFUL BECAUSE THERE'S SO MANY 3105 02:45:00,243 --> 02:45:02,578 CONVERSATIONS AND ISSUES BEHIND 3106 02:45:02,578 --> 02:45:04,180 THE SCENES WE DON'T HAVE ACCESS 3107 02:45:04,180 --> 02:45:06,415 TO THE INFORMATION THAT'S VERY 3108 02:45:06,415 --> 02:45:08,050 HELPFUL. 3109 02:45:08,050 --> 02:45:09,852 I THINK IF THERE'S PROMISING 3110 02:45:09,852 --> 02:45:11,053 FINDING WE COULD THINK AHEAD OF 3111 02:45:11,053 --> 02:45:16,726 TIME IN TERMS OF HOW TO 3112 02:45:16,726 --> 02:45:17,360 ACCELERATE THE PROCESS THROUGH 3113 02:45:17,360 --> 02:45:21,731 EARLY CONVERSATION AND THERE'S 3114 02:45:21,731 --> 02:45:24,500 LEGAL ISSUES AROUND THE SEQUENCE 3115 02:45:24,500 --> 02:45:28,137 FOR 101074 OR OTHER BNABS OR 3116 02:45:28,137 --> 02:45:29,905 OTHER SYSTEMS TAKING A LONG TIME 3117 02:45:29,905 --> 02:45:40,349 TO GET A CLEAR CUT ANSWER. 3118 02:45:41,250 --> 02:45:47,089 STANDARDIZING THE PROCESS AND 3119 02:45:47,089 --> 02:45:49,659 REALLY TAKING ADVANTAGE OF WHAT 3120 02:45:49,659 --> 02:45:51,327 ALL RIGHT EXISTS IN OTHER RARE 3121 02:45:51,327 --> 02:45:53,062 DISEASE SPACES, ETCETERA WOULD 3122 02:45:53,062 --> 02:45:59,568 BE MORE TIME EFFICIENT FOR US. 3123 02:45:59,568 --> 02:46:01,070 WE'RE LEARNING THROUGH THE 3124 02:46:01,070 --> 02:46:02,772 PROCESS AND COMING UP WITH A 3125 02:46:02,772 --> 02:46:04,273 PROCESS TO DO THIS. 3126 02:46:04,273 --> 02:46:06,976 HAVING EARLY ACCESS TO FUND TO 3127 02:46:06,976 --> 02:46:09,445 ACCELERATE THE PROCESS AS 3128 02:46:09,445 --> 02:46:11,013 SUGGESTED WHERE IF THERE'S HOPE 3129 02:46:11,013 --> 02:46:12,081 FOR CLINICAL TRIALS INSTEAD OF 3130 02:46:12,081 --> 02:46:20,823 HAVING TO APPLY FOR A GRANT AND 3131 02:46:20,823 --> 02:46:23,292 IT WOULD BE HELPFUL TO MOVE 3132 02:46:23,292 --> 02:46:24,160 THINGS FORWARD EXPEDITIOUSLY. 3133 02:46:24,160 --> 02:46:25,528 >> I WANT TO CALL ON PEOPLE IN 3134 02:46:25,528 --> 02:46:35,905 THE AUDIENCE TO HELP. 3135 02:46:36,906 --> 02:46:38,574 WE NEED HELP IN THE ROLE OF THE 3136 02:46:38,574 --> 02:46:41,043 ACTG AND THE WHOLE PROCESS. 3137 02:46:41,043 --> 02:46:41,711 >> I WANT TO COMMEND THE PANEL 3138 02:46:41,711 --> 02:46:43,212 AND TOPIC BECAUSE IT'S 3139 02:46:43,212 --> 02:46:43,612 IMPORTANT. 3140 02:46:43,612 --> 02:46:49,018 I WANT IT SHARE SINCE THERE'S 3141 02:46:49,018 --> 02:46:51,287 ATTENTION ON THE COMMENTS AND 3142 02:46:51,287 --> 02:46:53,856 WE'RE DRAFTING PART OF A LARGER 3143 02:46:53,856 --> 02:46:57,259 GROUP DRAFTING THE AIDS 3144 02:46:57,259 --> 02:46:59,362 PRIORITIES AND THAT TOPIC WAS 3145 02:46:59,362 --> 02:47:00,329 HIGHLIGHTED TO BE SINGULARLY 3146 02:47:00,329 --> 02:47:01,597 PLACED ON THE PRIORITIES MOVING 3147 02:47:01,597 --> 02:47:04,834 FORWARD TRYING TO INCENTIVIZE 3148 02:47:04,834 --> 02:47:07,436 INSTITUTES TO EXPAND ONGOING 3149 02:47:07,436 --> 02:47:07,670 EFFORTS. 3150 02:47:07,670 --> 02:47:10,606 NIAID ALREADY HAS SOME EFFORTS 3151 02:47:10,606 --> 02:47:13,509 IN THE AREA AND CARL CAN PERHAPS 3152 02:47:13,509 --> 02:47:16,345 COMMENT BUT TO EXPAND BUT THE 3153 02:47:16,345 --> 02:47:18,647 PIPELINE IS ALREADY NOTED LAS 3154 02:47:18,647 --> 02:47:23,419 BEEN SUCCESSFUL IN IDENTIFYING 3155 02:47:23,419 --> 02:47:27,423 MULTIPLE POTENTIAL AVENUES. 3156 02:47:27,423 --> 02:47:29,725 AND THE NCI HAS DONE IT 3157 02:47:29,725 --> 02:47:30,259 EFFICIENTLY WITH SEVERAL 3158 02:47:30,259 --> 02:47:31,660 PROGRAMS TO SUPPORT THE 3159 02:47:31,660 --> 02:47:33,963 PRODUCTION AND REGULATORY 3160 02:47:33,963 --> 02:47:36,198 INFRASTRUCTURE AND SUPPORT FOR 3161 02:47:36,198 --> 02:47:37,466 FDA MASTER FILINGS. 3162 02:47:37,466 --> 02:47:42,104 I THINK WE NEED THAT AS WE GROW 3163 02:47:42,104 --> 02:47:47,777 THE MDC EFFORT GOING FORWARD. 3164 02:47:47,777 --> 02:47:49,879 MIRE FROM THE PRIORITY OR 3165 02:47:49,879 --> 02:47:52,047 INVESTIGATOR SIDE WE CAN THEN 3166 02:47:52,047 --> 02:47:53,916 INCENTIVE SIZE MORE INSTITUTES 3167 02:47:53,916 --> 02:47:55,184 TO FOLLOW THAT EXAMPLE. 3168 02:47:55,184 --> 02:47:56,485 THE OTHER IS INDUSTRY 3169 02:47:56,485 --> 02:47:56,819 PARTNERSHIPS. 3170 02:47:56,819 --> 02:48:02,491 I THINK WE NEED TO BE MORE 3171 02:48:02,491 --> 02:48:05,161 DIALOGUE TO MAKE IT MORE 3172 02:48:05,161 --> 02:48:05,694 INCENTIVE I'D INDUSTRY 3173 02:48:05,694 --> 02:48:07,062 INVESTMENT IN THE ACADEMIC 3174 02:48:07,062 --> 02:48:08,164 EFFORT BECAUSE THEY HAVE 3175 02:48:08,164 --> 02:48:09,565 DIFFERENT PRESSURES AS NOTED. 3176 02:48:09,565 --> 02:48:13,869 THEY HAVE DIFFERENT PRIORITIES 3177 02:48:13,869 --> 02:48:14,804 REGARDING INTELLECTUAL PROPERTY 3178 02:48:14,804 --> 02:48:18,374 AND PROPERTY DEVELOPMENT 3179 02:48:18,374 --> 02:48:20,509 AND SOMETIMES WE THINK WOULDN'T 3180 02:48:20,509 --> 02:48:23,512 IT BE GREAT TO HAVE A AND B BUT 3181 02:48:23,512 --> 02:48:25,247 THERE'S NO WAY THEIR LAWYERS 3182 02:48:25,247 --> 02:48:27,817 WOULD AGREE AND COME UP WITH A 3183 02:48:27,817 --> 02:48:34,623 MODEL AND DIALOGUE TO WHAT WOULD 3184 02:48:34,623 --> 02:48:36,292 BE A MIDDLE GROUND. 3185 02:48:36,292 --> 02:48:39,228 WE AS ACADEMICS DON'T HAVE THE 3186 02:48:39,228 --> 02:48:40,930 PULL FOR THE FOLKS THAT MAKE THE 3187 02:48:40,930 --> 02:48:42,965 DECISIONS. 3188 02:48:42,965 --> 02:48:43,966 WE TALK TO INVESTIGATORS AND 3189 02:48:43,966 --> 02:48:45,701 THEY SAY IT'S A WONDERFUL IDEA 3190 02:48:45,701 --> 02:48:56,212 AND THEN WE HIT A BRICK WALL. 3191 02:48:57,546 --> 02:49:00,249 >> THE GATES FOUNDATION IS GOOD 3192 02:49:00,249 --> 02:49:01,951 AT ENCOURAGING THE INDUSTRY TO 3193 02:49:01,951 --> 02:49:02,184 DO THAT. 3194 02:49:02,184 --> 02:49:12,261 JOE. 3195 02:49:13,095 --> 02:49:15,831 >> THE PROCESS AND GETTING 3196 02:49:15,831 --> 02:49:17,867 SOMETHING UNIQUE FOR HIV OR 3197 02:49:17,867 --> 02:49:21,904 SPECIFIC THERE'S DISCUSSION 3198 02:49:21,904 --> 02:49:23,539 ABOUT SPECIFICITY. 3199 02:49:23,539 --> 02:49:27,543 THE PROBLEM WITH REPURPOSED 3200 02:49:27,543 --> 02:49:28,811 MOLECULES IS THE LACK OF 3201 02:49:28,811 --> 02:49:29,311 SPECIFICITY. 3202 02:49:29,311 --> 02:49:32,815 THE ACTG WON'T REALLY HELP 3203 02:49:32,815 --> 02:49:37,386 GETTING A MOLECULE FROM 3204 02:49:37,386 --> 02:49:37,987 SOMEONE'S LAB TO TOXICITY 3205 02:49:37,987 --> 02:49:39,722 INVOLVED AND THAT SORT OF THING. 3206 02:49:39,722 --> 02:49:43,459 MY REACTION IS IT'S SUCH AN 3207 02:49:43,459 --> 02:49:43,959 ENTREPRENEURIAL PROCESS. 3208 02:49:43,959 --> 02:49:47,429 THIS RISK THING. 3209 02:49:47,429 --> 02:49:50,900 PEOPLE ARE WILLING TO TAKE A 3210 02:49:50,900 --> 02:49:53,102 RISKING -- PEOPLE WITH MONEY, 3211 02:49:53,102 --> 02:49:54,069 MEANING, ARE WILLING TO TAKE A 3212 02:49:54,069 --> 02:50:01,877 RISK IF THEY CAN SEE A REWARD. 3213 02:50:01,877 --> 02:50:03,112 THE ALTRUISTIC REWARD IS NOT THE 3214 02:50:03,112 --> 02:50:13,656 SAME AS MON -- MONETARY REWARD. 3215 02:50:22,965 --> 02:50:27,436 MAYBE BNAB OR SIMPLER LIKE THIS 3216 02:50:27,436 --> 02:50:30,606 CD4 MEMETIC 3408 CULE WHICH 3217 02:50:30,606 --> 02:50:32,875 MAYBE TURNS PEOPLE'S OWN 3218 02:50:32,875 --> 02:50:38,147 ANTIBODY TO BNABS. 3219 02:50:38,147 --> 02:50:40,215 THE PRESENTATION WAS TREMENDOUS 3220 02:50:40,215 --> 02:50:41,250 FROM THE COLLABORATORY. 3221 02:50:41,250 --> 02:50:44,286 HOW CAN WE GET THOSE TO MOVE 3222 02:50:44,286 --> 02:50:45,554 FASTER? 3223 02:50:45,554 --> 02:50:50,759 WHAT THE ACTG DOES WELL IS WE'RE 3224 02:50:50,759 --> 02:50:51,827 GOOD AT THE COMPONENT PARTS AND 3225 02:50:51,827 --> 02:50:52,861 THE DATA PART. 3226 02:50:52,861 --> 02:50:58,367 WE HAVE OUTSTANDING DATA PART 3227 02:50:58,367 --> 02:51:03,272 AND EXCELLENT STATISTICAL 3228 02:51:03,272 --> 02:51:03,639 SUPPORT. 3229 02:51:03,639 --> 02:51:06,942 WE HAVE ENGAGED SITES AND WHERE 3230 02:51:06,942 --> 02:51:12,748 WE FALL DOWN IS WE DON'T REALLY 3231 02:51:12,748 --> 02:51:23,292 AND WE DON'T REALLY WOULD CAN'T 3232 02:51:38,007 --> 02:51:40,676 DO COMPLICATED TRIALS IN HUMANS 3233 02:51:40,676 --> 02:51:48,183 LIKE WE DO IN ANIMALS AND MICE. 3234 02:51:48,183 --> 02:51:54,757 WHAT'S THE PRIMARY GOAL AND WE 3235 02:51:54,757 --> 02:51:57,860 LOOK AT THIS AND THAT TERTIARY 3236 02:51:57,860 --> 02:51:58,827 OBJECTIVE AND THE WHOLE PROCESS 3237 02:51:58,827 --> 02:51:59,762 GETS CONFLATED AND WE DO THIS 3238 02:51:59,762 --> 02:52:10,005 ALL THE TIME. 3239 02:52:12,574 --> 02:52:14,610 TO SAY WHAT ASSAY YOU'LL DO ON 3240 02:52:14,610 --> 02:52:15,911 WHAT SPECIMEN AND HAVE THE 3241 02:52:15,911 --> 02:52:16,845 LABORATORY CENTER FIGURE THAT 3242 02:52:16,845 --> 02:52:21,316 OUT AND DEVELOP MTAs HOW YOU'LL 3243 02:52:21,316 --> 02:52:24,319 TRANSFER TO THE LAB IS ALL NUTS. 3244 02:52:24,319 --> 02:52:25,587 INSTEAD WE SHOULD DECIDE WHAT 3245 02:52:25,587 --> 02:52:27,222 THE PRIMARY OBJECTIVE IS. 3246 02:52:27,222 --> 02:52:29,558 WE CAN'T DEVELOP PROTOCOLS WE 3247 02:52:29,558 --> 02:52:30,292 COMMITTEE. 3248 02:52:30,292 --> 02:52:31,927 WE HAVE TO HAVE SOME CONSENSUS 3249 02:52:31,927 --> 02:52:33,696 FOR PROPOSALS. 3250 02:52:33,696 --> 02:52:37,933 WE HAVE TO HAVE PEER REVIEW 3251 02:52:37,933 --> 02:52:39,001 BECAUSE THAT'S WHAT THEY ARE 3252 02:52:39,001 --> 02:52:40,469 INSIST ON IS IMPORTANT AND HAVE 3253 02:52:40,469 --> 02:52:41,070 COMMUNITY INPUT. 3254 02:52:41,070 --> 02:52:47,242 ONCE THE IDEA IS FORMULATED AND 3255 02:52:47,242 --> 02:52:56,452 THERE'S AGREEMENT I MIGHT DO A 3256 02:52:56,452 --> 02:52:57,019 CONTROL TRIAL. 3257 02:52:57,019 --> 02:53:05,894 SO WE'RE NOT GOING TO GET 100% 3258 02:53:05,894 --> 02:53:11,467 AGREEMENT AND PMARINA HAS BEEN 3259 02:53:11,467 --> 02:53:21,977 FANTASTIC WITH THIS AND THEY 3260 02:53:27,483 --> 02:53:29,084 MOVED THE PROTOCOLS FASTER SO 3261 02:53:29,084 --> 02:53:34,323 WE'RE ALREADY GOING TO DO THAT. 3262 02:53:34,323 --> 02:53:37,926 THE FINAL THING IS WE PROBABLY 3263 02:53:37,926 --> 02:53:45,467 NEED TO BE MORE SPECIALIZED. 3264 02:53:45,467 --> 02:53:52,541 WE NEED RESOURCES AND COST THEM 3265 02:53:52,541 --> 02:53:57,513 APPROPRIATELY AND WE 3266 02:53:57,513 --> 02:54:02,151 DISINCENTIVIZE SITES. 3267 02:54:02,151 --> 02:54:04,686 AND WE'LL GIVE A STATIN OR 3268 02:54:04,686 --> 02:54:08,857 PLACEBO AND SEE IF IT WORKS. 3269 02:54:08,857 --> 02:54:15,430 THERE'S SO MUCH WORK CONSENTING 3270 02:54:15,430 --> 02:54:21,270 A PERSON AND THAT'S TIME THAT 3271 02:54:21,270 --> 02:54:31,947 HAS TO BE COMBPENSATED FOR AND 3272 02:54:34,516 --> 02:54:37,820 THE FINAL THING AND THE FINAL 3273 02:54:37,820 --> 02:54:39,621 THING IS WHAT KATIE SAID THE 3274 02:54:39,621 --> 02:54:40,589 COMPLEXITY AND ABILITY FOR 3275 02:54:40,589 --> 02:54:42,457 PEOPLE TO DO WHAT WE ASK THEM TO 3276 02:54:42,457 --> 02:54:46,595 DO IS INCREDIBLY HARD. 3277 02:54:46,595 --> 02:54:48,664 I HAD NOED A YA BUT WE TALKED 3278 02:54:48,664 --> 02:54:51,800 ABOUT IT AND SHE LIKED IT AND 3279 02:54:51,800 --> 02:54:55,704 JOHN LEE DIDN'T LIKE IT. 3280 02:54:55,704 --> 02:55:01,009 WE DO THE ATI PROTOCOLS AND TAKE 3281 02:55:01,009 --> 02:55:03,212 PEOPLE PERFECTLY HEALTHY WE'VE 3282 02:55:03,212 --> 02:55:04,847 NEVER MET AND CONVINCE THEM 3283 02:55:04,847 --> 02:55:07,749 MAYBE YOU WANT TO DO AN ATI 3284 02:55:07,749 --> 02:55:09,551 TRIAL AND DECIDE UP FRONT. 3285 02:55:09,551 --> 02:55:10,752 WHAT IF WE DIDN'T DECIDE UP 3286 02:55:10,752 --> 02:55:10,953 FRONT. 3287 02:55:10,953 --> 02:55:12,354 WHAT IF WE MADE THE ATI 3288 02:55:12,354 --> 02:55:21,330 OPTIONAL? 3289 02:55:21,330 --> 02:55:23,532 PEOPLE W.H.O. JOIN A STUDY LEARN 3290 02:55:23,532 --> 02:55:27,436 SO MUCH BEING PART OF A STUDY. 3291 02:55:27,436 --> 02:55:33,141 WHAT SANDY SAID ABOUT THE STUDY 3292 02:55:33,141 --> 02:55:33,809 WAS SO INFORMATIVE. 3293 02:55:33,809 --> 02:55:36,078 THEY WEREN'T GOING TO HAVE AN 3294 02:55:36,078 --> 02:55:37,946 ATI AND WHEN IT BECAME CLEAR 3295 02:55:37,946 --> 02:55:41,183 MAYBE WE SHOULD I THINK YOU SAID 3296 02:55:41,183 --> 02:55:43,952 EVERY SINGLE PERSON AGREED TO 3297 02:55:43,952 --> 02:55:45,120 HAVE AN ATI. 3298 02:55:45,120 --> 02:55:47,656 THEY ALREADY CONTRIBUTED AND 3299 02:55:47,656 --> 02:55:48,991 KNOW SOMETHING'S LAND AND 3300 02:55:48,991 --> 02:55:49,925 THEY'RE WILLING. 3301 02:55:49,925 --> 02:55:51,393 I THINK WE NEED TO BE A LITTLE 3302 02:55:51,393 --> 02:55:56,565 BIT MORE FLEXIBLE ON HOW WE 3303 02:55:56,565 --> 02:55:58,300 DESIGN OUR STUDIES AND THOSE ARE 3304 02:55:58,300 --> 02:56:01,236 SOME OF MY POSITIVE THOUGHTS 3305 02:56:01,236 --> 02:56:06,108 THAT ARE HOPEFULLY SOLUTION 3306 02:56:06,108 --> 02:56:06,475 ORIENTED. 3307 02:56:06,475 --> 02:56:07,109 THEN WE HAVE TO GO THROUGH THE 3308 02:56:07,109 --> 02:56:15,984 PROCESS. 3309 02:56:15,984 --> 02:56:20,389 FOR THE RECORD I DO LIKE 3310 02:56:20,389 --> 02:56:21,156 CONTROLLED STUDIES. 3311 02:56:21,156 --> 02:56:23,358 I ALWAYS TALK ABOUT THIS AND 3312 02:56:23,358 --> 02:56:25,661 PEOPLE GET ANNOYED AND I DON'T 3313 02:56:25,661 --> 02:56:26,895 KNOW WHY. 3314 02:56:26,895 --> 02:56:28,764 I LOOK AT THE VACCINE WORLD AND 3315 02:56:28,764 --> 02:56:31,233 I'M JEALOUS AND ENVIOUS AND 3316 02:56:31,233 --> 02:56:34,536 MAYBE IT'S NOT THE WAY IT WORK, 3317 02:56:34,536 --> 02:56:36,672 THEY DISCOVER THE IDEA AND CROSS 3318 02:56:36,672 --> 02:56:38,206 THE HALL AND KNOCKS ON THE DOOR 3319 02:56:38,206 --> 02:56:40,442 AND TOM KENNY MAKE A PRODUCT AND 3320 02:56:40,442 --> 02:56:43,845 THE BOTH CALL LARRY CORY AND THE 3321 02:56:43,845 --> 02:56:45,180 VTM LEADERSHIP AND WITHIN MONTHS 3322 02:56:45,180 --> 02:56:45,747 THEY HAVE SOMETHING IN THE 3323 02:56:45,747 --> 02:56:50,752 FIELD. 3324 02:56:50,752 --> 02:56:52,387 WE DON'T DO ANY OF THAT. 3325 02:56:52,387 --> 02:56:55,424 AND WE COULD. 3326 02:56:55,424 --> 02:57:02,264 I DON'T KNOW WHY. 3327 02:57:02,264 --> 02:57:04,566 >> THEY DECIDED WE NEEDED T CELL 3328 02:57:04,566 --> 02:57:07,936 IMMUNITY AND THEY LAD AN OUTCOME 3329 02:57:07,936 --> 02:57:11,974 T CELL IMMUNITY AND COULD DO 3330 02:57:11,974 --> 02:57:19,348 STUDIES THAT TOOK SIX MONTHS OR 3331 02:57:19,348 --> 02:57:19,982 LESS THIS SHOWED YOU CREATE T 3332 02:57:19,982 --> 02:57:26,822 CELL IMMUNITY AND OFF YOU GO. 3333 02:57:26,822 --> 02:57:34,663 YOU CAN DO STUDIES IN KIN DE 3334 02:57:34,663 --> 02:57:36,531 DERREN -- KINDERGARTEN AND WE 3335 02:57:36,531 --> 02:57:38,734 DON'T KNOW WHAT WE WANT TO DO. 3336 02:57:38,734 --> 02:57:42,237 DO WE WANT TO LOWER IPDA? 3337 02:57:42,237 --> 02:57:43,372 WE DON'T KNOW YET. 3338 02:57:43,372 --> 02:57:45,807 IT MAKES IT HARDER TO CRYSTALIZE 3339 02:57:45,807 --> 02:57:46,541 STUFF AND SAY THIS IS HOW WE 3340 02:57:46,541 --> 02:57:50,979 SHOULD DO IT. 3341 02:57:50,979 --> 02:57:52,047 I'M JEALOUS OF THEM TOO FOR LOTS 3342 02:57:52,047 --> 02:57:56,985 OF REASONS. 3343 02:57:56,985 --> 02:58:00,355 IF WE HAD A CONSENSUS FOR LRAs 3344 02:58:00,355 --> 02:58:10,866 IN HUMANS, DO WE NEED AN INT 3345 02:58:27,649 --> 02:58:27,916 INTERRUPTION. 3346 02:58:27,916 --> 02:58:38,393 >> WE KNOW WITH WHAT WE'RE 3347 02:58:52,340 --> 02:58:54,342 AFTER BUT DON'T KNOW THE 3348 02:58:54,342 --> 02:58:56,645 APPROACH AND IT SHOULD BE BASED 3349 02:58:56,645 --> 02:58:57,913 ON THE INTERESTING OPTION AND 3350 02:58:57,913 --> 02:59:01,116 WHICH ARE THE SPECIFIC 3351 02:59:01,116 --> 02:59:02,284 APPROACHES THAT SHOULD BE NOT 3352 02:59:02,284 --> 02:59:03,418 NECESSARILY TWO GROUPS BUT THE 3353 02:59:03,418 --> 02:59:12,260 APPROACH. 3354 02:59:12,260 --> 02:59:14,696 AND WORK WITH THE ACTG OR NOT TO 3355 02:59:14,696 --> 02:59:17,466 BRING IT TO LIFE. 3356 02:59:17,466 --> 02:59:26,007 BUT TO ME IT SHOULD BE APPROACH 3357 02:59:26,007 --> 02:59:36,184 FOCUSSED. 3358 02:59:39,321 --> 02:59:43,992 >> I'M A CARD CARRYING VACCINER 3359 02:59:43,992 --> 02:59:48,029 AN I BELIEVE IN EARLY STAGE 3360 02:59:48,029 --> 02:59:49,231 CANDIDATE FOR PHASE I STUDIES 3361 02:59:49,231 --> 02:59:53,468 BUT WE'RE LOOKING AT IMPACT ON 3362 02:59:53,468 --> 02:59:56,004 HUMAN LEATH AND THROUGH GET IT 3363 02:59:56,004 --> 02:59:58,974 THROUGH THE LARGER SCALE TRIALS 3364 02:59:58,974 --> 03:00:01,176 TO LICENSURE IS EXCEEDINGLY 3365 03:00:01,176 --> 03:00:01,977 COMPLEX ESPECIALLY IN THE 3366 03:00:01,977 --> 03:00:02,878 PREVENTION VACCINE SPACE. 3367 03:00:02,878 --> 03:00:05,413 YOU CANNOT DO THAT WITHOUT 3368 03:00:05,413 --> 03:00:07,015 INDUSTRY AND LARGE SCALE 3369 03:00:07,015 --> 03:00:07,716 INVESTMENT AND THAT'S BEEN 3370 03:00:07,716 --> 03:00:13,188 DIFFICULT TO GARNER FOR A 3371 03:00:13,188 --> 03:00:14,556 VARIETY OF REASONS. 3372 03:00:14,556 --> 03:00:17,325 THAT'S WHERE THE THERAPEUTIC 3373 03:00:17,325 --> 03:00:18,927 CURE FIELD HAS BETTER 3374 03:00:18,927 --> 03:00:21,029 OPPORTUNITY TO PARTNER WITH 3375 03:00:21,029 --> 03:00:22,898 INDUSTRY OR BETTER CHANCES OF 3376 03:00:22,898 --> 03:00:25,333 GETTING THOSE PARTNERSHIPS WHICH 3377 03:00:25,333 --> 03:00:27,435 IS PROBABLY AN ABOUT AS WELL TO 3378 03:00:27,435 --> 03:00:31,173 THE NEXT PANEL BECAUSE THERE'S A 3379 03:00:31,173 --> 03:00:35,644 MARKET OF DEFINED PEOPLE WHO 3380 03:00:35,644 --> 03:00:36,912 WOULD IMMEDIATELY EMBRACE AND 3381 03:00:36,912 --> 03:00:39,414 MANY PEOPLE IN THE ROOM SAID SO 3382 03:00:39,414 --> 03:00:41,883 THEMSELVES WE CAN LEVERAGE THAT 3383 03:00:41,883 --> 03:00:44,019 IN THE THERAPEUTIC SPACE TO WORK 3384 03:00:44,019 --> 03:00:45,954 TOWARDS THOSE INDUSTRY PARTNERS 3385 03:00:45,954 --> 03:00:51,993 FOR THE LARGER SCALE TRIALS. 3386 03:00:51,993 --> 03:00:54,329 >> THERE'S THE RELATIONSHIP OF 3387 03:00:54,329 --> 03:00:59,501 THE PARTICIPANTS IN THE STAFF 3388 03:00:59,501 --> 03:01:02,003 AND TAUGHT US COVID HOW 3389 03:01:02,003 --> 03:01:03,772 IMPORTANT THAT IS AT THE TOWN 3390 03:01:03,772 --> 03:01:06,341 HALL LAST NIGHT THERE WAS A 3391 03:01:06,341 --> 03:01:10,845 ROBUST DISCUSSION ABOUT TUSKEGEE 3392 03:01:10,845 --> 03:01:15,584 AND IT'S INTERESTING THERE'S 3393 03:01:15,584 --> 03:01:18,720 BEEN GROUP THREE ARE FROM 3394 03:01:18,720 --> 03:01:21,823 DESCENDANT OF THE TUSKEGEE 3395 03:01:21,823 --> 03:01:24,359 SURVIVE PUT TOGETHER AN AMAZING 3396 03:01:24,359 --> 03:01:33,868 PRESENTATION WHAT THE STUDY AND 3397 03:01:33,868 --> 03:01:35,136 CONS 3398 03:01:35,136 --> 03:01:37,839 CONSENT PROCESS AND HOW IT CAN 3399 03:01:37,839 --> 03:01:38,907 NEVER BE DONE AGAIN AND I'VE 3400 03:01:38,907 --> 03:01:40,909 BEEN DOING THIS WORK FOR A LONG 3401 03:01:40,909 --> 03:01:42,077 TIME IN TERMS OF THE SOCIAL 3402 03:01:42,077 --> 03:01:43,378 SCIENCES OF THE RESEARCH NEEDED 3403 03:01:43,378 --> 03:01:47,249 TO BRING PEOPLE UP TO SPEED TO 3404 03:01:47,249 --> 03:01:57,759 DESIGN TO HELP DESIGN TRIALS. 3405 03:02:02,063 --> 03:02:04,266 THERE'S LEGALESE NO ONE CAN USER 3406 03:02:04,266 --> 03:02:05,533 LIKE THE MICROSOFT END USER 3407 03:02:05,533 --> 03:02:05,834 ABREEMENT 3408 03:02:05,834 --> 03:02:08,703 IT AGREEMENT 3409 03:02:11,072 --> 03:02:11,373 AGREEMENT. 3410 03:02:11,373 --> 03:02:13,475 WE NEED TO REVISE THIS AND 3411 03:02:13,475 --> 03:02:16,678 THREES WE NEED TO RETHINK HOW WE 3412 03:02:16,678 --> 03:02:18,780 DO THIS AND WE HAVE SOME SOCIAL 3413 03:02:18,780 --> 03:02:22,450 BEHAVIOR RESEARCH HAPPENS IN A 3414 03:02:22,450 --> 03:02:27,822 HAPHAZARD MANNER. 3415 03:02:27,822 --> 03:02:30,392 AND I WOULD ARGUE WHAT WE NEED 3416 03:02:30,392 --> 03:02:35,430 IS AN EXTERNAL CORE WHERE WE 3417 03:02:35,430 --> 03:02:37,999 LEVERAGE ALL THE EXPERIENCE AND 3418 03:02:37,999 --> 03:02:40,368 ACROSS THE MULTIPLE 3419 03:02:40,368 --> 03:02:42,103 COLLABORATORIES OR NETWORKS. 3420 03:02:42,103 --> 03:02:44,572 THE MOST EFFICIENT WAY IS TO 3421 03:02:44,572 --> 03:02:47,075 HAVE AN EXTERNAL CORE TO TAP 3422 03:02:47,075 --> 03:02:51,413 INTO AS WE PROGRESS IN DESIGNING 3423 03:02:51,413 --> 03:02:52,213 THE TRIALS AND TURNING THIS FROM 3424 03:02:52,213 --> 03:03:02,490 BENCH TO BODIES. 3425 03:03:10,899 --> 03:03:16,304 >> I'LL SPEAK MORE ABOUT PRODUCT 3426 03:03:16,304 --> 03:03:16,538 ACCESS. 3427 03:03:16,538 --> 03:03:22,610 THAT'S NUMBER ONE HURDLE AND THE 3428 03:03:22,610 --> 03:03:26,381 VACCINE ENVY THEME. 3429 03:03:26,381 --> 03:03:28,616 WARE IN A BETTER POSITION 3430 03:03:28,616 --> 03:03:29,884 BECAUSE OUR CLINICAL TRIAL 3431 03:03:29,884 --> 03:03:33,388 TRIALS DON'T HAVE TO BE 3432 03:03:33,388 --> 03:03:34,723 GINORMOUS AND THAT'S EARN 3433 03:03:34,723 --> 03:03:37,792 AMAZING POSITION FOR US AS 3434 03:03:37,792 --> 03:03:39,961 CLINICAL TRIALISTS TO ESTABLISH 3435 03:03:39,961 --> 03:03:42,163 THE TRIALS WHICH ARE FAR HARDER 3436 03:03:42,163 --> 03:03:43,431 IN THE VACCINE WORLD. 3437 03:03:43,431 --> 03:03:47,669 LET'S REMEMBER THAT BEFORE WE 3438 03:03:47,669 --> 03:03:49,637 GET JEALOUS OF THE VACCINE 3439 03:03:49,637 --> 03:03:54,743 FIELD. 3440 03:03:54,743 --> 03:03:55,410 PARTNERSHIPS WE'RE BEING MAYBE A 3441 03:03:55,410 --> 03:03:57,112 LITTLE BIT NAIVE ABOUT THE 3442 03:03:57,112 --> 03:03:59,180 INDUSTRY PARTNERSHIP. 3443 03:03:59,180 --> 03:04:01,082 ACCESSING THROUGH AN INDUSTRY 3444 03:04:01,082 --> 03:04:02,050 PARTNERSHIP IS INCREDIBLY HARD. 3445 03:04:02,050 --> 03:04:04,185 MOST THE PRODUCTS WE WANT HAVE 3446 03:04:04,185 --> 03:04:06,521 NOT BEEN DEVELOPED FOR HIV AND 3447 03:04:06,521 --> 03:04:09,491 THEREFORE THOSE INDUSTRIES ARE 3448 03:04:09,491 --> 03:04:11,192 NOT REALLY INTERESTED IN FIRST 3449 03:04:11,192 --> 03:04:13,862 OF ALL HAVING ACCESS LET ALONE 3450 03:04:13,862 --> 03:04:18,400 FUNDING OF OTHER PRODUCTS. 3451 03:04:18,400 --> 03:04:23,405 AND I'VE HAD EXPERIENCES WITH 3452 03:04:23,405 --> 03:04:25,540 ABBVIE AND BOTH HAVE BEEN 3453 03:04:25,540 --> 03:04:27,575 DIFFICULT PROCESSES BECAUSE 3454 03:04:27,575 --> 03:04:28,376 NEITHER COMPANY CARES TOO MUCH 3455 03:04:28,376 --> 03:04:31,379 ABOUT HIV BUT HAVE A LICENSED 3456 03:04:31,379 --> 03:04:38,052 PRODUCT AND EASIEST THING HAS 3457 03:04:38,052 --> 03:04:46,528 BEEN PURCHASE THE ENVOLMAB. 3458 03:04:46,528 --> 03:04:50,832 AND EVEN IF LICENSED YOU CAN 3459 03:04:50,832 --> 03:04:53,301 ACCESS IT BUT NEED MONEY WITHOUT 3460 03:04:53,301 --> 03:04:56,938 HAVING TO WORK WITH AN INDUSTRY 3461 03:04:56,938 --> 03:04:58,573 PARTNER WOULD BE ADVANTAGEOUS 3462 03:04:58,573 --> 03:05:00,809 BECAUSE THE INDUSTRY PARTNER IN 3463 03:05:00,809 --> 03:05:02,677 THE END WON'T HAVE AN ACTIVE 3464 03:05:02,677 --> 03:05:03,511 ROLE BECAUSE THEY'RE NOT TRYING 3465 03:05:03,511 --> 03:05:08,950 TO DEVELOP A PRODUCT FOR HIV. 3466 03:05:08,950 --> 03:05:14,856 THE SECOND PART IS ANTIBODIES 3467 03:05:14,856 --> 03:05:17,759 AND I THINK CONTRACTS FOR 3468 03:05:17,759 --> 03:05:18,393 MANUFACTURERS COULD BE A GOOD 3469 03:05:18,393 --> 03:05:26,434 WAY TO GO. 3470 03:05:26,434 --> 03:05:28,102 AND THEY MADE ANTIBODIES UNDER 3471 03:05:28,102 --> 03:05:38,279 CONTRACT. 3472 03:05:42,183 --> 03:05:44,052 AND SOME HAVE BEEN ABLE TO 3473 03:05:44,052 --> 03:05:44,786 DEVELOP ANTIBODIES VERY FAST AND 3474 03:05:44,786 --> 03:05:51,426 CAN WE DO MORE WITH THE VRC. 3475 03:05:51,426 --> 03:05:53,728 >> JULIAN YOU HAVE THE LAST WORD 3476 03:05:53,728 --> 03:05:54,963 SO MAKE IT GOOD. 3477 03:05:54,963 --> 03:05:56,564 >> GREAT COMMENT. 3478 03:05:56,564 --> 03:06:03,972 I WOULD SHARE AN OBSERVATION AND 3479 03:06:03,972 --> 03:06:07,709 MAYBE A SUGGESTION. 3480 03:06:07,709 --> 03:06:15,450 BEFORE HIV ARPA-H WE TALKED 3481 03:06:15,450 --> 03:06:18,186 ABOUT GETTING MORE PROSECUTES 3482 03:06:18,186 --> 03:06:19,821 GMP MANUFACTURER AVAILABLE FOR 3483 03:06:19,821 --> 03:06:21,789 CLINICAL TESTING. 3484 03:06:21,789 --> 03:06:24,526 THIS A COMBHON KWHLG AND OUR 3485 03:06:24,526 --> 03:06:29,631 COLLEAGUES ARE TAPPING INTO A 3486 03:06:29,631 --> 03:06:40,074 NUMBER OF WAYS THERE'S A 3487 03:06:53,321 --> 03:06:56,057 GENERATION AND AS EITHER FIELD 3488 03:06:56,057 --> 03:06:58,860 BRINGS PRODUCTS INTO IND 3489 03:06:58,860 --> 03:07:02,196 ENABLING STUDIES AND GMP, THAT 3490 03:07:02,196 --> 03:07:03,431 COMMON SITUATIONAL AWARENESS 3491 03:07:03,431 --> 03:07:08,770 EARLY I THINK COULD BE VERY 3492 03:07:08,770 --> 03:07:14,509 HELPFUL BECAUSE SUBSEQUENT 3493 03:07:14,509 --> 03:07:20,848 ACCESS TO PRODUCTS AND 3494 03:07:20,848 --> 03:07:22,317 COORDINATED PLANNING FOR ACCESS 3495 03:07:22,317 --> 03:07:28,256 IN THE CURE AND VACCINE SPACES 3496 03:07:28,256 --> 03:07:30,325 AS PRODUCTS MOVE TO MANUFACTURE 3497 03:07:30,325 --> 03:07:34,295 CAN BE HELPFUL. 3498 03:07:34,295 --> 03:07:39,367 THERE ARE ALREADY SOME COMBINED 3499 03:07:39,367 --> 03:07:43,771 CURE VACCINE CURE PRE 3500 03:07:43,771 --> 03:07:44,372 PRESENTATION GRANTS ALL RIGHT. 3501 03:07:44,372 --> 03:07:48,910 THAT COLLABORATIVE SPIRIT 3502 03:07:48,910 --> 03:07:50,244 BETWEEN BOTH FIELDS COULD BE 3503 03:07:50,244 --> 03:07:51,913 HELPFUL DOWN THE ROAD. 3504 03:07:51,913 --> 03:07:52,480 HOPEFULLY THAT WAS HELPFUL. 3505 03:07:52,480 --> 03:07:55,617 >> THANK YOU. 3506 03:07:55,617 --> 03:07:59,053 SO WE'LL GO AHEAD AND END NOW. 3507 03:07:59,053 --> 03:08:00,955 WE'VE BEEN BASHING INDUSTRY THE 3508 03:08:00,955 --> 03:08:01,990 LAST HOUR FOR NOT DOING THEIR 3509 03:08:01,990 --> 03:08:02,190 PART. 3510 03:08:02,190 --> 03:08:04,225 SO THEY'LL HAVE A CHANCE NOW TO 3511 03:08:04,225 --> 03:08:05,693 GET BACK AT US. 3512 03:08:05,693 --> 03:08:10,732 I THINK THEY HAVE THE NEXT 3513 03:08:10,732 --> 03:08:10,932 PANEL. 3514 03:08:10,932 --> 03:08:13,534 SANDY, ANY FINAL WORDS? 3515 03:08:13,534 --> 03:08:13,735 OKAY. 3516 03:08:13,735 --> 03:08:24,145 THANKS A LOT, EVERYONE. 3517 03:09:14,128 --> 03:09:16,931 >> DEPRIVING THE ROLES OF 3518 03:09:16,931 --> 03:09:18,933 RESPONSIBILITIES AND 3519 03:09:18,933 --> 03:09:19,500 UNDERSTANDING PRIORITIES. 3520 03:09:19,500 --> 03:09:21,703 THIS IS WHAT I TALKED ABOUT BUT 3521 03:09:21,703 --> 03:09:23,304 I'LL LEAVE IT TO THE PANELISTS 3522 03:09:23,304 --> 03:09:28,976 TO TELL US AND WE HAVE SOME 3523 03:09:28,976 --> 03:09:33,514 QUESTIONS UP HERE TO GUIDE YOU 3524 03:09:33,514 --> 03:09:35,817 AND WE HAVE PEOPLE JOINING US 3525 03:09:35,817 --> 03:09:36,417 ONLINE IF YOU CAN SPOTLIGHT 3526 03:09:36,417 --> 03:09:38,052 THEM. 3527 03:09:38,052 --> 03:09:43,191 THANK YOU. 3528 03:09:43,191 --> 03:09:51,132 >> THANK YOU, UUDAJ AND THE 3529 03:09:51,132 --> 03:09:52,667 OPPORTUNITY TO SPEAK ABOUT THE 3530 03:09:52,667 --> 03:09:53,434 COLLABORATORIES AND THE CURRENT 3531 03:09:53,434 --> 03:09:56,070 PRIZE AS A WHOLE. 3532 03:09:56,070 --> 03:10:03,644 I'M RICK DUNHAM WITH VIIV AND 3533 03:10:03,644 --> 03:10:10,952 LEAD THE IMMUNIOLOGY PROGRAM 3534 03:10:10,952 --> 03:10:13,855 AND STARTED AS A POSTDOC IN THE 3535 03:10:13,855 --> 03:10:16,290 ORIGINAL DARE AND COMING THROUGH 3536 03:10:16,290 --> 03:10:18,626 THE CARE COLLABORATORY AS AN 3537 03:10:18,626 --> 03:10:20,461 INDUSTRY PARTNER EMBEDDED IN THE 3538 03:10:20,461 --> 03:10:25,500 LABS AT UNC AND THEN NOW WORKING 3539 03:10:25,500 --> 03:10:27,301 AS PART OF THE EXECUTIVE 3540 03:10:27,301 --> 03:10:28,202 COMMITTEE ON PAVE. 3541 03:10:28,202 --> 03:10:30,772 I HAVE PERHAPS A UNIQUE 3542 03:10:30,772 --> 03:10:33,374 PERSPECTIVE SITTING IN ALL THE 3543 03:10:33,374 --> 03:10:36,244 POSSIBLE ROLES EXCEPT FOR AT THE 3544 03:10:36,244 --> 03:10:43,151 NIH I GUESS AT THIS POINT. 3545 03:10:43,151 --> 03:10:45,052 THE ROLE MUCH INDUSTRY IN THE 3546 03:10:45,052 --> 03:10:46,954 DELANEY COLLABORATORY WAS 3547 03:10:46,954 --> 03:10:48,523 ENVISIONED IN THE ORIGINAL 3548 03:10:48,523 --> 03:10:51,092 SCIENCE PAPER I BELIEVE 2009 3549 03:10:51,092 --> 03:10:52,860 WHERE THIS ROLE -- THIS 3550 03:10:52,860 --> 03:10:54,262 THREE-WAY COLLABORATION BETWEEN 3551 03:10:54,262 --> 03:10:55,329 INDUSTRY, GOVERNMENT AND 3552 03:10:55,329 --> 03:10:57,999 ACADEMIA WAS ENVISIONED WHERE 3553 03:10:57,999 --> 03:11:00,701 EACH WAS BRINGING THEIR 3554 03:11:00,701 --> 03:11:03,404 EXPERTISE TO THE TABLE AND EACH 3555 03:11:03,404 --> 03:11:06,941 GAINING FROM THE WORK TOGETHER 3556 03:11:06,941 --> 03:11:07,809 TO BETTER THE SCIENCE OF HIV 3557 03:11:07,809 --> 03:11:10,144 YOU'RE AND BRINGING MEDICINES 3558 03:11:10,144 --> 03:11:10,378 FORWARD. 3559 03:11:10,378 --> 03:11:14,248 AND THIS IS REALLY I THINK BEEN 3560 03:11:14,248 --> 03:11:17,218 REASONABLY WELL EXECUTED DESPITE 3561 03:11:17,218 --> 03:11:20,721 THE OBVIOUS SHORT COMINGS THAT 3562 03:11:20,721 --> 03:11:24,892 ARE ALWAYS GOING TO BE PRESENT 3563 03:11:24,892 --> 03:11:34,001 IN THIS TYPE OF PORK -- 3564 03:11:34,001 --> 03:11:40,374 PORCUPINE SETTING AND THERE'S 3565 03:11:40,374 --> 03:11:45,580 COLLABORATORIES OVER YEARS IN 3566 03:11:45,580 --> 03:11:50,051 TARGET SCREENS AND VALIDATION 3567 03:11:50,051 --> 03:11:52,620 EXERCISES AND REPURPOSED DRUGS, 3568 03:11:52,620 --> 03:11:53,221 ETCETERA. 3569 03:11:53,221 --> 03:11:55,323 I THINK IT'S BEEN PRETTY 3570 03:11:55,323 --> 03:11:55,690 SUCCESSFUL. 3571 03:11:55,690 --> 03:12:05,399 I THINK STEVE YOU UNDERESTIMATE 3572 03:12:05,399 --> 03:12:05,900 THE INVESTMENT IN THE 3573 03:12:05,900 --> 03:12:06,868 COLLABORATORY SPACE. 3574 03:12:06,868 --> 03:12:08,903 IT'S IMPORTANT TO RECOGNIZE 3575 03:12:08,903 --> 03:12:09,103 THAT. 3576 03:12:09,103 --> 03:12:10,404 THE INVESTMENT IT'S REQUIRED TO 3577 03:12:10,404 --> 03:12:20,882 BRING THESE INTO THE SPACE. 3578 03:12:37,632 --> 03:12:41,369 JENNIFER IS THE CO CHAIR SO 3579 03:12:41,369 --> 03:12:43,037 INTRODUCING YOURSELF AND 3580 03:12:43,037 --> 03:12:45,239 EXAMPLES OF HOW THE 3581 03:12:45,239 --> 03:12:46,440 COLLABORATORIES HAVE WORKED AND 3582 03:12:46,440 --> 03:12:47,742 COME BACK TO TRY TO BRAIN STORM 3583 03:12:47,742 --> 03:12:50,111 ON THE BARRIERS AND HOW TO COME 3584 03:12:50,111 --> 03:12:50,645 ACROSS THE BARRIERS. 3585 03:12:50,645 --> 03:12:52,280 JENNIFER. 3586 03:12:52,280 --> 03:12:53,014 >> THANKS, RICK. 3587 03:12:53,014 --> 03:12:55,416 CAN YOU HEAR ME? 3588 03:12:55,416 --> 03:12:57,485 >> YES. 3589 03:12:57,485 --> 03:13:07,395 >> I'M JEN GORDON CHIEF OFFICER 3590 03:13:07,395 --> 03:13:09,563 AT EXCISION THERAPEUTIC FOUNDED 3591 03:13:09,563 --> 03:13:15,603 AT TEM -- TEMPLE AND SPENT MY 3592 03:13:15,603 --> 03:13:17,505 CAREER IN ACADEMIA. 3593 03:13:17,505 --> 03:13:20,908 I CAN SPEAK TO BOTH SIDES OF THE 3594 03:13:20,908 --> 03:13:23,811 FENCE SO TO SPEAK. 3595 03:13:23,811 --> 03:13:26,514 I THINK WE HEARD A LOT EXAMPLES 3596 03:13:26,514 --> 03:13:29,517 IN THE EARLY STAGES OF HOW 3597 03:13:29,517 --> 03:13:32,286 INDUSTRY AND ACADEMIC 3598 03:13:32,286 --> 03:13:33,521 PARTNERSHIPS ARE WORKING I THINK 3599 03:13:33,521 --> 03:13:38,893 THE CHALLENGE AND I HOPE WE'LL 3600 03:13:38,893 --> 03:13:49,403 TALK ABOUT THAT TODAY IS AND 3601 03:13:52,740 --> 03:13:58,045 HAVE PLATFORMS LIKE NDC AND 3602 03:13:58,045 --> 03:13:59,780 INDUSTRY IS WORKING TOGETHER AND 3603 03:13:59,780 --> 03:14:02,016 WE OFTEN HAVE DIFFERENT GOALS 3604 03:14:02,016 --> 03:14:03,684 AND VISIONS AND THERE'S A LACK 3605 03:14:03,684 --> 03:14:05,286 OF RESOURCES ESPECIALLY IN THE 3606 03:14:05,286 --> 03:14:06,620 VALLEY OF DEATH. 3607 03:14:06,620 --> 03:14:07,922 THE CHALLENGES ARE VERY 3608 03:14:07,922 --> 03:14:10,224 DIFFERENT FOR BIG PHARMA VERSUS 3609 03:14:10,224 --> 03:14:11,058 THE SMALL BIO TECH. 3610 03:14:11,058 --> 03:14:12,593 I HOPE WE CAN FOCUS ON THAT 3611 03:14:12,593 --> 03:14:13,227 DURING OUR DISCUSSION TODAY AS 3612 03:14:13,227 --> 03:14:21,802 WELL. 3613 03:14:21,802 --> 03:14:26,941 >> I'LL CALL ON CARL NEXT. 3614 03:14:26,941 --> 03:14:31,412 >> CAN YOU HEAR ME? 3615 03:14:31,412 --> 03:14:32,013 >> YES. 3616 03:14:32,013 --> 03:14:38,052 >> I'M CARL BALIBAR AND BEEN 3617 03:14:38,052 --> 03:14:41,555 ACROSS NOVARTIS AND MERCK. 3618 03:14:41,555 --> 03:14:46,060 RECENTLY WORKING IN THE HIV 3619 03:14:46,060 --> 03:14:46,527 CURES SPACE. 3620 03:14:46,527 --> 03:14:47,762 I REPRESENT A BROADER TEAM IN 3621 03:14:47,762 --> 03:14:54,268 OUR DISCOVERY GROUP THAT IS 3622 03:14:54,268 --> 03:14:58,406 COLLABORATING WITH THE NBC AN 3623 03:14:58,406 --> 03:15:07,148 CARE, ERASE, GRID AND I THINK WE 3624 03:15:07,148 --> 03:15:10,251 HAVE A LOT OF EXCITING 3625 03:15:10,251 --> 03:15:11,085 CONTRIBUT 3626 03:15:11,085 --> 03:15:12,820 CONTRIBUTIONS AND INTERACTIONS 3627 03:15:12,820 --> 03:15:13,454 AROUND TECHNOLOGY DEVELOPMENT 3628 03:15:13,454 --> 03:15:15,022 AND VALIDATION. 3629 03:15:15,022 --> 03:15:17,425 WE HAVE DEVELOPED ULTRA 3630 03:15:17,425 --> 03:15:25,866 SENSITIVE ASSAYS SUCH AS P24, 3631 03:15:25,866 --> 03:15:27,668 SAMOA AND APPLIED THOSE THROUGH 3632 03:15:27,668 --> 03:15:31,072 OUR RESEARCH. 3633 03:15:31,072 --> 03:15:35,409 WE'VE WORKED ON THE AT HOME 3634 03:15:35,409 --> 03:15:36,544 BLOOD COLLECTIVE DEVICE WHICH 3635 03:15:36,544 --> 03:15:39,080 CAN BE USEFUL IN ENABLING 3636 03:15:39,080 --> 03:15:39,914 RESEARCH WHERE PEOPLE DON'T HAVE 3637 03:15:39,914 --> 03:15:43,784 TO GO TO THE CLINIC REGULARLY 3638 03:15:43,784 --> 03:15:53,694 AND STE IF THEY'RE CURED. 3639 03:15:53,694 --> 03:16:00,768 ARE AND IT'S TESTED HYPOTHESES 3640 03:16:00,768 --> 03:16:02,069 AND CONTRIBUTE TO THE FIELD AT 3641 03:16:02,069 --> 03:16:10,444 LARGE. 3642 03:16:10,444 --> 03:16:12,313 >> CAN YOU HEAR ME? 3643 03:16:12,313 --> 03:16:15,416 >> PERFECT. 3644 03:16:15,416 --> 03:16:19,019 I'M ELENA VENDRAME AT GILEAD AND 3645 03:16:19,019 --> 03:16:20,054 I'VE BEEN THERE ABOUT FIVE YEARS 3646 03:16:20,054 --> 03:16:25,259 AND MOSTLY WORKING ON HIV CURE 3647 03:16:25,259 --> 03:16:26,026 CLINICAL TRIALS. 3648 03:16:26,026 --> 03:16:29,330 I GUESS TO HIGHLIGHT A LITTLE 3649 03:16:29,330 --> 03:16:32,099 BIT WHAT OUR COLLABORATION HAS 3650 03:16:32,099 --> 03:16:34,902 BEEN WOVE HAD SEVERAL OVER THE 3651 03:16:34,902 --> 03:16:37,638 YEARS AND HAVE MANY 3652 03:16:37,638 --> 03:16:42,743 COLLABORATIONS OUTSIDE OF THE 3653 03:16:42,743 --> 03:16:47,114 NETWORKS THAT EITHER OUTGOING OR 3654 03:16:47,114 --> 03:16:49,250 CLEATED OVER TIME. 3655 03:16:49,250 --> 03:16:54,255 THE MAIN CONTRIBUTE HAS BEEN 3656 03:16:54,255 --> 03:16:58,859 SCIENTIFIC ADVICE AS WELL 3657 03:16:58,859 --> 03:17:01,729 PROVIDING DRUG PRODUCT FOR 3658 03:17:01,729 --> 03:17:05,099 DIFFERENT STUDIES ON THE NPH 3659 03:17:05,099 --> 03:17:11,438 SIDE FOR MODELS OR IMP AGONISTS 3660 03:17:11,438 --> 03:17:21,749 FOR DISH STUDIES. 3661 03:17:22,183 --> 03:17:31,192 >> I'M AT IMMUNITY BIO WHICH HAS 3662 03:17:31,192 --> 03:17:32,726 CHALLENGES AS DIFFERENCES WITH 3663 03:17:32,726 --> 03:17:37,331 BIO TECH AND BIG PHARMA WITH 3664 03:17:37,331 --> 03:17:39,233 RESPECT TO PARTICIPATING IN 3665 03:17:39,233 --> 03:17:40,401 ACADEMIC RESEARCH, ETCETERA. 3666 03:17:40,401 --> 03:17:43,304 I WOULD SAY I WOULDN'T BE HERE 3667 03:17:43,304 --> 03:17:47,274 IF IT WASN'T FOR OUR ABILITY TO 3668 03:17:47,274 --> 03:17:49,677 HAVE WORKED IN THE PAST WITH OUR 3669 03:17:49,677 --> 03:17:52,079 ACADEMIC COLLEAGUES AND THE NDC 3670 03:17:52,079 --> 03:17:54,315 BECAUSE HAVE BEEN VERY 3671 03:17:54,315 --> 03:17:59,887 SUCCESSFUL AT BEING ABLE TO GET 3672 03:17:59,887 --> 03:18:04,291 THE PRODUCT TO THE MDCs FOR 3673 03:18:04,291 --> 03:18:06,293 PRECLINICAL MODELS AND IN THE 3674 03:18:06,293 --> 03:18:07,194 CLINIC FOR HIV STUDIES. 3675 03:18:07,194 --> 03:18:11,131 IT'S A TESTAMENT TO THE 3676 03:18:11,131 --> 03:18:15,436 DILIGENCE OF OUR PARTNERS. 3677 03:18:15,436 --> 03:18:21,542 IMMUNITY BIO DOESN'T HAVE AN 3678 03:18:21,542 --> 03:18:24,078 INFECTIOUS DISEASE LABORATORY SO 3679 03:18:24,078 --> 03:18:25,646 EVERYTHING WE DO IS BY NATURE IS 3680 03:18:25,646 --> 03:18:30,451 A COLLABORATION. 3681 03:18:30,451 --> 03:18:40,928 IT HAS IT'S OWN CHALLENGES. 3682 03:18:59,780 --> 03:19:02,850 IF WE CAN MOVE OUR SUPER AGONIST 3683 03:19:02,850 --> 03:19:06,053 CLINICALLY AND PRE CLINICALLY IN 3684 03:19:06,053 --> 03:19:08,222 THE HIV SPACE AND VACCINE SPACE 3685 03:19:08,222 --> 03:19:10,090 AS AN ADJUVANT, FOR EXAMPLE. 3686 03:19:10,090 --> 03:19:12,426 I'LL STOP THERE AND THEN I THINK 3687 03:19:12,426 --> 03:19:14,094 WE'LL TALK ABOUT OTHER ISSUES AS 3688 03:19:14,094 --> 03:19:19,433 WE MOVE FORWARD. 3689 03:19:19,433 --> 03:19:25,606 >> I'M ONE OF THE FOUNDERS OF 3690 03:19:25,606 --> 03:19:26,106 ACCELAVIR. 3691 03:19:26,106 --> 03:19:29,076 WE'RE KIND OF DIFFERENT. 3692 03:19:29,076 --> 03:19:30,144 WE'RE A SMALL COMPANY AND 3693 03:19:30,144 --> 03:19:34,114 MORPHED INTO RAY CRO FOCUSSED ON 3694 03:19:34,114 --> 03:19:36,116 MOLECULAR ASSAY DEVELOPMENT 3695 03:19:36,116 --> 03:19:39,153 GENOMICS AN ASSAY DEVELOPMENT 3696 03:19:39,153 --> 03:19:41,021 BROADLY ACROSS GENE THERAPY AND 3697 03:19:41,021 --> 03:19:41,989 HAVE BEEN FOCUSSED ON HIV 3698 03:19:41,989 --> 03:19:43,590 RESEARCH AND YOU'RE FOR A WHILE. 3699 03:19:43,590 --> 03:19:46,327 MY BACKGROUND AS A STUDENT 14 3700 03:19:46,327 --> 03:19:48,896 YEARS AGO IN BOB'S LAB AND THE 3701 03:19:48,896 --> 03:19:52,132 WORK HAS BEEN FOCUSSED ON HIV. 3702 03:19:52,132 --> 03:19:54,435 I THINK OUR ROLE HAS BEEN AS A 3703 03:19:54,435 --> 03:20:03,177 RESEARCH FACILITATOR AND PARTNER 3704 03:20:03,177 --> 03:20:06,313 THOSE THAT DON'T HAVE IPDA OR 3705 03:20:06,313 --> 03:20:08,115 THE VIRAL SEQUENCING APPROACHES 3706 03:20:08,115 --> 03:20:13,020 GROUPS ARE APPLYING NOW. 3707 03:20:13,020 --> 03:20:15,456 WE HAVE INTERVENTIONAL AND 3708 03:20:15,456 --> 03:20:16,824 OBSERVATIONAL CLINICAL STUDIES. 3709 03:20:16,824 --> 03:20:19,393 I FEEL LIKE WE'RE BECOMING A 3710 03:20:19,393 --> 03:20:21,662 WEALTH OF KNOWLEDGE HOW TO 3711 03:20:21,662 --> 03:20:22,796 IMPLEMENT THESE ASSAYS AT SCALE 3712 03:20:22,796 --> 03:20:25,065 YOU NEED FOR A CLINICAL STUDY 3713 03:20:25,065 --> 03:20:27,167 AND HOW TO INTERPRET DATA OR 3714 03:20:27,167 --> 03:20:29,036 WHAT TIME POINTS AND BLOOD 3715 03:20:29,036 --> 03:20:30,304 VOLUME REQUIREMENTS YOU NEED TO 3716 03:20:30,304 --> 03:20:35,743 CONSIDER WHEN YOU SCOPE AN 3717 03:20:35,743 --> 03:20:35,943 ASSAY. 3718 03:20:35,943 --> 03:20:46,487 I THINK ONE THERE'S AREAS WHERE 3719 03:21:00,701 --> 03:21:01,268 WE SEE OPPORTUNITY FOR THE 3720 03:21:01,268 --> 03:21:02,669 DELANEY COLLABORATORIES TO WORK 3721 03:21:02,669 --> 03:21:06,073 MORE EFFICIENTLY. 3722 03:21:06,073 --> 03:21:08,075 THERE'S RESOURCE GAPS LABS 3723 03:21:08,075 --> 03:21:09,877 STRUGGLE WITH WELL CHARACTERIZED 3724 03:21:09,877 --> 03:21:12,179 MATERIALS OR ACCESS TO SAMPLES 3725 03:21:12,179 --> 03:21:15,149 OR ANIMAL MODELS I THINK WE 3726 03:21:15,149 --> 03:21:20,087 COULD HELP FACILITATE AND 3727 03:21:20,087 --> 03:21:26,093 CERTAINLY WE'VE SEEN EFFORTS 3728 03:21:26,093 --> 03:21:28,028 ACROSS COLLABORATORIES THAT ARE 3729 03:21:28,028 --> 03:21:28,896 DUPLICATIVE. 3730 03:21:28,896 --> 03:21:29,897 TO A DISCUSSION IN THE PREVIOUS 3731 03:21:29,897 --> 03:21:32,900 PANEL IF WE CAN HELP FACILITATE 3732 03:21:32,900 --> 03:21:35,235 OPPORTUNITIES FOR DIVERSE GROUPS 3733 03:21:35,235 --> 03:21:38,505 AS AN ASSAY PARTNER TO HELP AC 3734 03:21:38,505 --> 03:21:39,239 SEGREGATE TOWARDS CLINICAL TRIAL 3735 03:21:39,239 --> 03:21:40,641 I THINK THAT WOULD BE AN 3736 03:21:40,641 --> 03:21:43,844 EXCITING PLACE FOR US TO BE MORE 3737 03:21:43,844 --> 03:21:50,117 IMPACTFUL. 3738 03:21:50,117 --> 03:21:55,389 >> SO VII V IS WORKING ON A 3739 03:21:55,389 --> 03:21:56,557 COMPREHENSIVE PORTFOLIO TO 3740 03:21:56,557 --> 03:21:58,358 PROVIDE LONG LIVED IMMUNITY TO 3741 03:21:58,358 --> 03:22:07,434 THE VIRUS TO ENABLE ART-FREE VIR 3742 03:22:07,434 --> 03:22:12,940 OWE LOGIC -- VIROLOGIC AND 3743 03:22:12,940 --> 03:22:14,341 THERE'S GOOD WORK TO DO 3744 03:22:14,341 --> 03:22:14,641 TOGETHER. 3745 03:22:14,641 --> 03:22:18,512 WE HAVE SOME GOOD EXAMPLES OF 3746 03:22:18,512 --> 03:22:19,580 DOING THAT. 3747 03:22:19,580 --> 03:22:22,616 I'LL HIGHLIGHT WHAT SEEMS 3748 03:22:22,616 --> 03:22:25,586 MUNDANE TO EVERYBODY BUT THE 3749 03:22:25,586 --> 03:22:27,454 PROVISION OF ANTIRETROVIRAL 3750 03:22:27,454 --> 03:22:30,657 DRUGS FOR MONKEY STUDIES IS NOT 3751 03:22:30,657 --> 03:22:31,925 TRIVIAL TO PROVIDE JUST THE 3752 03:22:31,925 --> 03:22:37,097 INFRASTRUCTURE FOR ALL THESE 3753 03:22:37,097 --> 03:22:39,333 STUDIES AND HIGHLIGHT THE WORK 3754 03:22:39,333 --> 03:22:42,603 WE DID IN COLLABORATION WITH UNC 3755 03:22:42,603 --> 03:22:47,908 AND MEMORY TO BRING FORWARD TO 3756 03:22:47,908 --> 03:22:58,352 DO THE TARGET VALIDATION. 3757 03:23:02,122 --> 03:23:03,924 AND HAVE OBJECTIVES OF PHARMA 3758 03:23:03,924 --> 03:23:07,427 AND ACADEMIA THAT CAME TOGETHER 3759 03:23:07,427 --> 03:23:13,000 IN A UNIQUE WAY. 3760 03:23:13,000 --> 03:23:15,869 TO MAKE REAL PROGRESS IN NOVEL 3761 03:23:15,869 --> 03:23:17,204 LATENCY REVERSING AGENT. 3762 03:23:17,204 --> 03:23:19,039 THAT WAS UNIQUE. 3763 03:23:19,039 --> 03:23:24,077 WE MADE A LOT OF PROGRESS THERE 3764 03:23:24,077 --> 03:23:31,451 AND THOSE ALSO HIGHLIGHT THE 3765 03:23:31,451 --> 03:23:34,888 BARRIERS FOR OTHER PAR GETS AN 3766 03:23:34,888 --> 03:23:36,590 MODALITIES TO LINE THE TIMING 3767 03:23:36,590 --> 03:23:38,158 HAS TO ALIGN IN PARTICULAR IT'S 3768 03:23:38,158 --> 03:23:43,463 VERY DIFFICULT TO ALIGN THE 3769 03:23:43,463 --> 03:23:48,368 TIMING OF AN INDUSTRY WITH THE 3770 03:23:48,368 --> 03:23:51,438 TIMING OF COLLABORATORY GRANTS 3771 03:23:51,438 --> 03:23:52,940 WRITTEN FOR NEXT FIVE YEAR 3772 03:23:52,940 --> 03:23:53,640 PERIOD, FOR INSTANCE. 3773 03:23:53,640 --> 03:23:56,109 AND THE INCENTIVES HAVE TO WORK 3774 03:23:56,109 --> 03:23:58,679 AT THE RIGHT TIME AND THAT DRUG 3775 03:23:58,679 --> 03:23:59,313 DISCOVERY PROGRAM WITH RESPECT 3776 03:23:59,313 --> 03:24:09,690 TO THE COLLABORATORY. 3777 03:24:13,427 --> 03:24:16,630 ARE THERE KEY BARRIERS THAT 3778 03:24:16,630 --> 03:24:18,565 PREVENT THEM OR THEIR GROUPS OR 3779 03:24:18,565 --> 03:24:20,300 OTHER GROUPS FROM GOING DEEPER 3780 03:24:20,300 --> 03:24:23,437 INTO COLLABORATIONS HERE. 3781 03:24:23,437 --> 03:24:24,571 DOES ANYONE WANT TO TAKE A FIRST 3782 03:24:24,571 --> 03:24:34,781 STEP THERE. 3783 03:24:52,265 --> 03:24:55,702 >> AND THERE'S A STIMULATOR AND 3784 03:24:55,702 --> 03:24:57,638 EVERYONE KNOWS IL-15 ALONE WILL 3785 03:24:57,638 --> 03:25:02,109 CURE HIV. 3786 03:25:02,109 --> 03:25:07,280 SO HOW DO WE PICK AND CHOOSE 3787 03:25:07,280 --> 03:25:08,281 BENEFITS TO BE THE BEST. 3788 03:25:08,281 --> 03:25:09,149 IT'S NOT EASY. 3789 03:25:09,149 --> 03:25:12,152 I'M CHARGED EVERY DAY BY OUR 3790 03:25:12,152 --> 03:25:14,154 CEO -- HE WANTS TO SEE THE NEXT 3791 03:25:14,154 --> 03:25:21,495 TRIAL THAT HAS A COMBINATION AND 3792 03:25:21,495 --> 03:25:23,597 I NEED IT NAME IT TOMORROW AND I 3793 03:25:23,597 --> 03:25:24,998 CAN'T BECAUSE THE COMBINATIONS 3794 03:25:24,998 --> 03:25:26,767 WE WOULD LIKE TO DO ARE STILL 3795 03:25:26,767 --> 03:25:29,069 BEING INVESTIGATED IN AND OF 3796 03:25:29,069 --> 03:25:32,105 THEMSELVES TO AALLOW THEM TO GET 3797 03:25:32,105 --> 03:25:38,111 TO THE STAGE WHERE IT MAKES 3798 03:25:38,111 --> 03:25:41,148 SENSE TO COMBINE THEM WITH OUR 3799 03:25:41,148 --> 03:25:42,883 SUPER AGONIST AND CREATES 3800 03:25:42,883 --> 03:25:45,252 PROBLEMS WHEN A TRIAL NEEDS 3801 03:25:45,252 --> 03:25:48,889 MULTI-FACTORIAL COMBINATIONS OF 3802 03:25:48,889 --> 03:25:49,790 DIFFERENT AGENT MANY OF WHICH 3803 03:25:49,790 --> 03:25:54,561 ARE OWNED BY DIFFERENT ENTITIES 3804 03:25:54,561 --> 03:25:57,397 THE INTELLECTUAL PROPERTY ISSUES 3805 03:25:57,397 --> 03:25:59,433 COME TO THE FRONT BEFORE IT 3806 03:25:59,433 --> 03:26:07,441 COMES TO THE FRONT. 3807 03:26:07,441 --> 03:26:09,910 AND WHO ACCESS OF WHO IS COMING 3808 03:26:09,910 --> 03:26:11,511 TO THE TRIAL AND THEY'RE IN THE 3809 03:26:11,511 --> 03:26:14,114 SIMPLE QUESTIONS AND IN SOME 3810 03:26:14,114 --> 03:26:19,453 TRIALS THE COMBINATIONS ARE NOT 3811 03:26:19,453 --> 03:26:23,323 FOR EXAMPLE TRIAL WITH ACTG AND 3812 03:26:23,323 --> 03:26:27,461 USING ANTIBODIES LICENSED BY 3813 03:26:27,461 --> 03:26:29,396 GILEAD PLUS OR MOLECULE. 3814 03:26:29,396 --> 03:26:31,965 THERE NEEDED TO BE AN AGREEMENT 3815 03:26:31,965 --> 03:26:41,742 TO DO BOTH STUDIES. 3816 03:26:41,742 --> 03:26:44,111 AND IF YOU ADD THREE OR FOUR 3817 03:26:44,111 --> 03:26:49,649 OTHER MOLECULES OR ENTITIES INTO 3818 03:26:49,649 --> 03:26:55,689 THAT MIX AND I'D LOVE A SOLUTION 3819 03:26:55,689 --> 03:27:01,027 COMING TO THE TABLE FOR 3820 03:27:01,027 --> 03:27:01,895 INTELLECTUAL PROPERTY CONCERNS 3821 03:27:01,895 --> 03:27:03,964 THAT MAKES IT DIFFICULT TO AGREE 3822 03:27:03,964 --> 03:27:04,998 HOW TO MOVE FORWARD BECAUSE IT'S 3823 03:27:04,998 --> 03:27:15,375 NOT ALWAYS THAT CLEAR. 3824 03:27:20,413 --> 03:27:24,384 >> EACH ENTITY HAS TO BE PUT 3825 03:27:24,384 --> 03:27:27,621 TOGETHER AND THE DEVELOPMENT 3826 03:27:27,621 --> 03:27:28,655 PARADIGMS REQUIRE A LOT OF 3827 03:27:28,655 --> 03:27:30,857 INVESTMENT SO UNLESS YOU HAVE 3828 03:27:30,857 --> 03:27:32,125 LINE OF SIGHT IT'S HARD TO MAKE 3829 03:27:32,125 --> 03:27:35,028 THE INVESTMENTS TO MULTIPLE 3830 03:27:35,028 --> 03:27:37,297 TARGETS WITH THE THOUGHT LATER 3831 03:27:37,297 --> 03:27:44,805 ON THEY CAN ALL BE COMBINED. 3832 03:27:44,805 --> 03:27:45,906 IS THERE STILL A PRODUCT WITH 3833 03:27:45,906 --> 03:27:47,107 REMAINING ONES IF THERE'S A 3834 03:27:47,107 --> 03:27:50,610 SAFETY SIGNAL THAT COMES UP WHEN 3835 03:27:50,610 --> 03:27:52,312 YOU START COMBINING THINGS 3836 03:27:52,312 --> 03:27:53,413 TOGETHER THAT CAN PREVENT 3837 03:27:53,413 --> 03:27:55,615 PROGRESSION AND CLINICAL 3838 03:27:55,615 --> 03:28:01,388 DEVELOPMENT. 3839 03:28:01,388 --> 03:28:02,889 IT'S UNLIKELY THE OCCUR'S GOING 3840 03:28:02,889 --> 03:28:06,960 TO COME FROM A SINGLE AGENT AND 3841 03:28:06,960 --> 03:28:08,762 IT REQUIRES A LOT OF INVESTMENT. 3842 03:28:08,762 --> 03:28:10,764 I THINK THAT'S WHERE DIFFERENT 3843 03:28:10,764 --> 03:28:13,767 COMPANIES COMBINE BUT AS JUST 3844 03:28:13,767 --> 03:28:14,835 POINTED OUT THOSE COMBINATIONS 3845 03:28:14,835 --> 03:28:15,735 OR PRIOR AGREEMENTS CAN BE 3846 03:28:15,735 --> 03:28:20,273 DIFFICULT TO PUT TOGETHER. 3847 03:28:20,273 --> 03:28:20,740 WHEREIN A. 3848 03:28:20,740 --> 03:28:27,447 IT WAN BE HARD TO TAKE AN ASSET 3849 03:28:27,447 --> 03:28:30,083 FROM ONE THERAPY AREA TO ANOTHER 3850 03:28:30,083 --> 03:28:34,454 AND THERE'S BEEN STUDIES WITH PD 3851 03:28:34,454 --> 03:28:39,926 1 AND MERCK HAS A MOLE MOL KWUL 3852 03:28:39,926 --> 03:28:42,262 AND PEOPLE WANT TO RE -- 3853 03:28:42,262 --> 03:28:43,697 MOLECULE AND PEOPLE WANT TO 3854 03:28:43,697 --> 03:28:47,701 REPURPOSE IT FOR HIV AND IT'S 3855 03:28:47,701 --> 03:28:50,003 OWNED BY THE ONCOLOGY PART OF 3856 03:28:50,003 --> 03:28:50,203 MERCK. 3857 03:28:50,203 --> 03:28:57,344 THEY HAVE ULTIMATE RIGHTS TO 3858 03:28:57,344 --> 03:28:58,945 WHETHER IT CAN BE USED IN 3859 03:28:58,945 --> 03:29:01,248 DIFFERENT TRIALS AND PURPOSES. 3860 03:29:01,248 --> 03:29:04,651 IT'S NOT AS IS SIMPLE AS SAYING 3861 03:29:04,651 --> 03:29:07,988 SOMEBODY OWNS THE ASSETS. 3862 03:29:07,988 --> 03:29:09,356 IT'S MORE COMPLICATED AND THAT 3863 03:29:09,356 --> 03:29:12,726 COULD BE A BARRIER AS WELL. 3864 03:29:12,726 --> 03:29:17,163 AND WE TRY TO ENABLE AS BEST WE 3865 03:29:17,163 --> 03:29:19,733 CAN WITH PD 1 WHAT WE'VE DONE IN 3866 03:29:19,733 --> 03:29:22,402 COLLABORATION WITH MDC IS TAKING 3867 03:29:22,402 --> 03:29:25,572 TOOLS FROM EARLIER STAGES OF THE 3868 03:29:25,572 --> 03:29:28,108 PROGRAM AND ARE ABLE TO DO BASIC 3869 03:29:28,108 --> 03:29:31,912 RESEARCH IN ANIMAL MODELS AND WE 3870 03:29:31,912 --> 03:29:35,448 PUBLISHED ON THOSE RESULTS 3871 03:29:35,448 --> 03:29:39,452 LOOKING AT PD 1 AND IL-10 FOR 3872 03:29:39,452 --> 03:29:40,587 RESERVOIR CONTROL AFTER 3873 03:29:40,587 --> 03:29:41,187 INTERRUPTION. 3874 03:29:41,187 --> 03:29:42,856 THAT'S WHERE WE TRY TO 3875 03:29:42,856 --> 03:29:46,893 CONTRIBUTE EVEN WHEN WE MIGHT BE 3876 03:29:46,893 --> 03:29:54,234 ABLE TO PROVIDE A CLINICAL 3877 03:29:54,234 --> 03:29:54,734 ASSET. 3878 03:29:54,734 --> 03:29:58,204 >> THERE'S DEVELOPING THE 3879 03:29:58,204 --> 03:30:01,942 COMPONENTS OF COMBINATIONS IN 3880 03:30:01,942 --> 03:30:03,243 ADDITION TO BEING TIME CONSUMING 3881 03:30:03,243 --> 03:30:05,111 IT'S NOT VERY SEXY. 3882 03:30:05,111 --> 03:30:09,049 THAT WON'T BE INCLUDED IN THE 3883 03:30:09,049 --> 03:30:11,451 GRANT PROPOSAL TO TAKE THE 3884 03:30:11,451 --> 03:30:13,119 SINGLE AGENT THROUGH ITS DOSE 3885 03:30:13,119 --> 03:30:17,457 FINDING TOXICOLOGY STUDIES. 3886 03:30:17,457 --> 03:30:20,293 AND THAT FALLS SOLELY IN THE 3887 03:30:20,293 --> 03:30:23,196 PHARMA DOMAIN TO BRING INTO THE 3888 03:30:23,196 --> 03:30:26,266 PROOF OF CONCEPT EFFICACY BASED 3889 03:30:26,266 --> 03:30:32,138 STUDIES. 3890 03:30:32,138 --> 03:30:36,943 THAT'S A BARRIER TO GET TO THE 3891 03:30:36,943 --> 03:30:37,744 EFFICACY STUDIES. 3892 03:30:37,744 --> 03:30:42,615 >> TO BUILD ON WHAT WAS SAID SO 3893 03:30:42,615 --> 03:30:47,420 FAR I COMPLEEPTLY AGREE ON THE 3894 03:30:47,420 --> 03:30:50,857 CHALLENGE -- COMPLETELY AGREE ON 3895 03:30:50,857 --> 03:30:54,160 PUTTING TOGETHER MULTI-PARTY 3896 03:30:54,160 --> 03:30:56,696 AGREEMENT AND HOW DO WE 3897 03:30:56,696 --> 03:30:58,365 PRIORITIZE FOR REQUESTS FOR THE 3898 03:30:58,365 --> 03:31:05,772 SAME DRUG FOR CLINICAL STUDY AND 3899 03:31:05,772 --> 03:31:07,841 WOULD LIKE TO PROVIDE A DRUG TO 3900 03:31:07,841 --> 03:31:09,342 EVERYONE WHO ASKS FOR IT BUT 3901 03:31:09,342 --> 03:31:14,581 HAVE TO BE MINDFUL OF WHAT WE 3902 03:31:14,581 --> 03:31:17,517 HAVE COMMITTED TO AND HAVE TO 3903 03:31:17,517 --> 03:31:24,557 PRIORITIZE THE BIGGEST DATA GAP 3904 03:31:24,557 --> 03:31:26,126 OR UNMET NEEDS AND FACED WITH 3905 03:31:26,126 --> 03:31:36,002 CHALLENGES. 3906 03:31:36,002 --> 03:31:39,239 >> RELATED TO THAT WE HEARD HOW 3907 03:31:39,239 --> 03:31:40,106 TO ENCOURAGE INDUSTRY IT TAKE 3908 03:31:40,106 --> 03:31:41,574 MORE RISK BUT MAY BE IT'S REALLY 3909 03:31:41,574 --> 03:31:44,611 THE OPPOSITE. 3910 03:31:44,611 --> 03:31:47,047 HOW TO HELP INDUSTRY DERISK AND 3911 03:31:47,047 --> 03:31:48,782 PROVIDE SUPPORT FOR THESE TYPES 3912 03:31:48,782 --> 03:31:50,150 OF ACTIVITIES. 3913 03:31:50,150 --> 03:31:52,452 AND WHAT KIND OF ROLE COULD NIH 3914 03:31:52,452 --> 03:31:53,586 PLAY IN PROVIDING THAT. 3915 03:31:53,586 --> 03:31:55,021 WE HEARD ABOUT THE CHALLENGES 3916 03:31:55,021 --> 03:31:56,122 WITH CMC. 3917 03:31:56,122 --> 03:32:02,128 I THINK THIS WOULD FIT IN THE 3918 03:32:02,128 --> 03:32:06,533 SAME CATEGORY. 3919 03:32:06,533 --> 03:32:07,600 AND PROVIDE FOR THE BIG GAP IN 3920 03:32:07,600 --> 03:32:17,744 BETWEEN. 3921 03:32:34,060 --> 03:32:36,763 >> AND MAYBE WE LOOK AT KILLING 3922 03:32:36,763 --> 03:32:39,365 EFFICACY STUDIES AND SOMETHING 3923 03:32:39,365 --> 03:32:41,067 AT LEAST WAS NEW TO ME AS 3924 03:32:41,067 --> 03:32:43,136 SOMEONE TRANSITIONING FROM 3925 03:32:43,136 --> 03:32:45,238 ACADEMIC SIDES TO MORE INDUSTRY 3926 03:32:45,238 --> 03:32:46,439 ORIENTED SIDES. 3927 03:32:46,439 --> 03:32:48,942 THAT'S A LESSON THE FIELD COULD 3928 03:32:48,942 --> 03:32:51,311 MAYBE TAKE SETTING A MORE 3929 03:32:51,311 --> 03:32:53,480 STRUCTURED MILESTONE DRIVEN 3930 03:32:53,480 --> 03:32:54,380 MECHANISM FOR ESSENTIALLY 3931 03:32:54,380 --> 03:32:56,850 KILLING IDEAS THAT ARE EXCITING 3932 03:32:56,850 --> 03:32:58,518 IN PAPERS BUT MAYBE DON'T HAVE 3933 03:32:58,518 --> 03:32:59,819 THE CAPACITY TO PROGRESS TO 3934 03:32:59,819 --> 03:33:02,589 CLINICAL STUDIES. 3935 03:33:02,589 --> 03:33:07,760 I'VE HEARD A LOT OF DISCUSSION 3936 03:33:07,760 --> 03:33:18,271 TODAY ABOUT WHEN WE NEED AND 3937 03:33:25,512 --> 03:33:28,915 HAVE CANDIDATES THAT PROGRESS 3938 03:33:28,915 --> 03:33:30,049 MIGHT BE MORE EFFICIENT. 3939 03:33:30,049 --> 03:33:33,052 AND WOULD MIRROR THE DE RISKING 3940 03:33:33,052 --> 03:33:37,223 JEN AND OTHERS COMMENTED ON THE 3941 03:33:37,223 --> 03:33:37,857 PRECLINICAL THINGS ADVANCE TO 3942 03:33:37,857 --> 03:33:48,134 PHASE 1 STUDIES. 3943 03:33:56,576 --> 03:34:00,813 >> IN THE PAST SOME APPLICATIONS 3944 03:34:00,813 --> 03:34:02,515 HAD A JOINT IP AGREEMENT ACROSS 3945 03:34:02,515 --> 03:34:04,617 INDUSTRY PARTNERS. 3946 03:34:04,617 --> 03:34:06,252 I DON'T KNOW HOW MANY 3947 03:34:06,252 --> 03:34:07,520 COLLABORATORIES NOW HAVE SUCH 3948 03:34:07,520 --> 03:34:13,426 AGREEMENTS OR HAVE DONE THOSE 3949 03:34:13,426 --> 03:34:13,660 THINGS. 3950 03:34:13,660 --> 03:34:15,094 IS THAT SOMETHING THAT CHANGED 3951 03:34:15,094 --> 03:34:17,497 AND THINGS HAVE MOVED. 3952 03:34:17,497 --> 03:34:19,966 IS THAT SOMETHING THAT'S STILL 3953 03:34:19,966 --> 03:34:20,466 CONCEIVABLY POSSIBLE? 3954 03:34:20,466 --> 03:34:25,738 WOULD IT BE POSSIBLE TO SET UP 3955 03:34:25,738 --> 03:34:28,408 SUCH A JOINT AGREEMENT FOR A 3956 03:34:28,408 --> 03:34:30,777 COLLABORATORY OR TROOPS EVEN OH, 3957 03:34:30,777 --> 03:34:32,412 MY GOD ACROSS THE ENTIRE 3958 03:34:32,412 --> 03:34:33,646 COLLABORATORY PROGRAM. 3959 03:34:33,646 --> 03:34:35,782 I'M JUST REMEMBERING THE WORK 3960 03:34:35,782 --> 03:34:43,856 THAT THE GROUPS DID FOR THE DRUG 3961 03:34:43,856 --> 03:34:46,192 REQUEST AND NOT SURE HOW MUCH 3962 03:34:46,192 --> 03:34:47,427 THAT GOT USED THOUGH IT TOOK 3963 03:34:47,427 --> 03:34:50,863 YEARS TO DEVELOP. 3964 03:34:50,863 --> 03:34:52,832 IS THERE ANOTHER WAY TO THINK 3965 03:34:52,832 --> 03:34:54,367 ABOUT WAYS TO THINK ABOUT THE 3966 03:34:54,367 --> 03:34:55,335 HURDLES OR KEEP DOING OUR BEST 3967 03:34:55,335 --> 03:35:03,109 AS WE HAVE BEEN? 3968 03:35:03,109 --> 03:35:05,078 >> ANYBODY WANT TO JUMP IN AND 3969 03:35:05,078 --> 03:35:07,847 COMMENT ON DAVE'S QUESTION? 3970 03:35:07,847 --> 03:35:10,350 >> IT'S EASY TO DO THAT IN THE 3971 03:35:10,350 --> 03:35:12,352 BEGINNING OF AN MDC IF YOU 3972 03:35:12,352 --> 03:35:14,153 IDENTIFY THE COMPOUNDS YOU WANT 3973 03:35:14,153 --> 03:35:20,360 TO USE IN YOUR TRIAL. 3974 03:35:20,360 --> 03:35:24,030 IT'S EASY. 3975 03:35:24,030 --> 03:35:25,598 YOU PROBABLY HAVE WRITTEN YOUR 3976 03:35:25,598 --> 03:35:29,602 GRANT APPLICATION WITH A 3977 03:35:29,602 --> 03:35:31,504 PARTICULAR COMPOUND IN MIND AND 3978 03:35:31,504 --> 03:35:34,440 GOTTEN A LETTER OF SUPPORT TO DO 3979 03:35:34,440 --> 03:35:35,475 THAT IN THE GRANT APPLICATION. 3980 03:35:35,475 --> 03:35:36,843 THAT'S THE EASY PART. 3981 03:35:36,843 --> 03:35:47,420 THE FIRST AGREEMENT THAT HAPPENS 3982 03:35:47,420 --> 03:35:57,497 IS A MULTI-PARTY NON-DISCLOSURE 3983 03:35:57,497 --> 03:36:02,769 AGREEMENT AND MAYBE AND MAYBE TO 3984 03:36:02,769 --> 03:36:06,072 THINK ABOUT THAT RATHER THAN 3985 03:36:06,072 --> 03:36:11,544 JUST RELYING ON AN NDA TO GET 3986 03:36:11,544 --> 03:36:16,816 THINGS STARTED. 3987 03:36:16,816 --> 03:36:23,456 IF YOU HAVE A SET IDEA OF WHAT 3988 03:36:23,456 --> 03:36:24,724 COMPOUNDS YOU'RE TRYING TO USE 3989 03:36:24,724 --> 03:36:29,028 YOU KNOW WHERE YOUR GOING AND IF 3990 03:36:29,028 --> 03:36:30,930 YOU KNOW WHERE YOU'RE GOING THE 3991 03:36:30,930 --> 03:36:33,499 ROAD IS EASIER. 3992 03:36:33,499 --> 03:36:38,171 >> I'LL ADD IN PRINCIPLE IF 3993 03:36:38,171 --> 03:36:40,340 POSSIBLE EACH COMPANY AND EACH 3994 03:36:40,340 --> 03:36:41,841 INSTITUTION APPLIES A DIFFERENT 3995 03:36:41,841 --> 03:36:44,210 LENS TO ESTABLISHING THOSE 3996 03:36:44,210 --> 03:36:46,846 AGREEMENTS SPEAKING MORE FROM 3997 03:36:46,846 --> 03:36:52,251 THE COMPANY LOOKING OUT 3998 03:36:52,251 --> 03:36:57,857 PERSPECTIVE NOW AND SOME 3999 03:36:57,857 --> 03:37:00,126 INSTITUTIONS ARE VERY BROAD IN 4000 03:37:00,126 --> 03:37:02,195 TERMS OF THE DRUGS WE'RE 4001 03:37:02,195 --> 03:37:04,330 PROVIDING EVEN AS JUST AN 4002 03:37:04,330 --> 03:37:05,531 ANTIRETROVIRAL AS THE PART OF 4003 03:37:05,531 --> 03:37:09,535 THE BACKBONE AND PART OF THE 4004 03:37:09,535 --> 03:37:11,838 INVESTIGATIVE WORK FOR THE RIGHT 4005 03:37:11,838 --> 03:37:13,206 TO OWN INTELLECTUAL PROPERTY ON 4006 03:37:13,206 --> 03:37:15,441 THE DRUGS WE'RE TRYING TO 4007 03:37:15,441 --> 03:37:17,777 PROVIDE FOR THE STUDIES. 4008 03:37:17,777 --> 03:37:19,779 IT'S ACTUALLY VERY DIFFICULT 4009 03:37:19,779 --> 03:37:25,651 FROM OUR PERSPECTIVE AS ACQU 4010 03:37:25,651 --> 03:37:26,219 ACQUIRERS OF INTELLECTUAL 4011 03:37:26,219 --> 03:37:27,186 PROPERTY TO DO THE STUDIES. 4012 03:37:27,186 --> 03:37:34,160 >> THERE'S A LEDGER ON THE OTHER 4013 03:37:34,160 --> 03:37:36,429 SIDE THE APPLICATION IS TO GET 4014 03:37:36,429 --> 03:37:40,233 FEDERAL FUNDS AND THEY ARE MAKE 4015 03:37:40,233 --> 03:37:41,300 CERTAIN REQUIREMENTS TO GET THE 4016 03:37:41,300 --> 03:37:41,968 FEDERAL FUNDS. 4017 03:37:41,968 --> 03:37:44,904 AGAIN, IT'S A HIGH LEVEL 4018 03:37:44,904 --> 03:37:46,773 DISCUSSION BUT MAYBE SOMETHING 4019 03:37:46,773 --> 03:37:51,444 TO THINK ABOUT. 4020 03:37:51,444 --> 03:38:01,888 WE WANT TO TRY TO MOVE FORWARD 4021 03:38:01,888 --> 03:38:07,427 AND THINK OF A COLLABORATIVE 4022 03:38:07,427 --> 03:38:09,796 AGREEMENT FOR A COLLABORATORY. 4023 03:38:09,796 --> 03:38:12,999 >> IT MAY DEPEND ON THE STAGE OF 4024 03:38:12,999 --> 03:38:15,001 THE ASSET AND THE MORE SPECIFIC 4025 03:38:15,001 --> 03:38:16,669 AGREEMENT IS THE BETTER THE 4026 03:38:16,669 --> 03:38:19,672 CHANCE WHEN IT'S REALLY BROAD 4027 03:38:19,672 --> 03:38:23,409 IT'S HARD FOR AN INDUSTRY 4028 03:38:23,409 --> 03:38:27,180 PARTNER TO DECIDE ON RIGHTS IN 4029 03:38:27,180 --> 03:38:28,481 THE DISCOVERY SPACE YEARS BEFORE 4030 03:38:28,481 --> 03:38:30,883 IT EVER GOES TO THE CLINIC. 4031 03:38:30,883 --> 03:38:33,486 IF THERE'S AN ASSET SOMEONE 4032 03:38:33,486 --> 03:38:35,421 WANTS TO PARTNER WITH SOMETHING 4033 03:38:35,421 --> 03:38:38,591 ELSE THEN THOSE AGREEMENTS 4034 03:38:38,591 --> 03:38:42,995 BECOME MORE TANGIBLE. 4035 03:38:42,995 --> 03:38:44,230 IT'S A LITTLE EASIER TO 4036 03:38:44,230 --> 03:38:45,598 UNDERSTAND WHAT THE ASK IS UP 4037 03:38:45,598 --> 03:38:46,232 FRONT OF AND THERE'S LESS RISK I 4038 03:38:46,232 --> 03:38:47,633 THINK. 4039 03:38:47,633 --> 03:38:51,938 >> AND TO ADD TO THAT I THINK 4040 03:38:51,938 --> 03:38:52,839 ULTIMATELY AN AGREEMENT IS EASY 4041 03:38:52,839 --> 03:38:55,942 TO PUT IN PLACE IF THERE'S A 4042 03:38:55,942 --> 03:38:59,579 COMMON MISSION BETWEEN THE PA 4043 03:38:59,579 --> 03:39:05,384 PARTIES THAT ENTER THE AGREEMENT 4044 03:39:05,384 --> 03:39:07,153 AND EVALUATE THE PROJECT ON ITS 4045 03:39:07,153 --> 03:39:09,121 OWN AND WHAT QUESTION IS 4046 03:39:09,121 --> 03:39:11,524 ANSWERING IS SOMETIMES KEY TO BE 4047 03:39:11,524 --> 03:39:15,428 ABLE TO OVERCOME SOME OF THE IP 4048 03:39:15,428 --> 03:39:16,729 ISSUES AND GENERALLY SPEAKING 4049 03:39:16,729 --> 03:39:19,732 WE'RE ALL I THINK IN FAVOR OF 4050 03:39:19,732 --> 03:39:22,134 TRYING TO COLLABORATE MORE AND 4051 03:39:22,134 --> 03:39:24,670 FIND NEW WAYS OF OVERCOMING THE 4052 03:39:24,670 --> 03:39:25,605 HURDLES BUT SOMETIMES THE 4053 03:39:25,605 --> 03:39:27,440 SPECIFICS ARE NEEDED TO ENTER 4054 03:39:27,440 --> 03:39:37,884 INTO A SPECIFIC AGREEMENT. 4055 03:39:39,719 --> 03:39:42,655 >> I'M SIDNEY A Ph.D. STUDENT 4056 03:39:42,655 --> 03:39:44,257 WIN THE ERASE COLLABORATORY. 4057 03:39:44,257 --> 03:39:47,660 I RUN A MONKEY STUDIO AND HAD 4058 03:39:47,660 --> 03:39:51,430 THE PLEASURE OF WORKING WITH 4059 03:39:51,430 --> 03:39:53,299 INDUSTRY PARTNERS WHETHER 4060 03:39:53,299 --> 03:39:56,269 ANTIRETROVIRALS OR COMPOUNDS. 4061 03:39:56,269 --> 03:39:57,737 WE HEARD A LOT OF DISCUSSION 4062 03:39:57,737 --> 03:39:59,438 ABOUT IP RIGHTS. 4063 03:39:59,438 --> 03:40:01,674 AS WE MOVE CLOSER TO A THERAPY 4064 03:40:01,674 --> 03:40:04,810 FOR A CURE AS MY STUDY HAS SHOWN 4065 03:40:04,810 --> 03:40:06,546 WE NEEDED SEVERAL COMPOUNDS NORD 4066 03:40:06,546 --> 03:40:08,548 TO SEE REDUCTION IN THE 4067 03:40:08,548 --> 03:40:14,220 RESERVOIR FOR INTACT DNA. 4068 03:40:14,220 --> 03:40:16,989 HOW DOES INDUSTRY SEE 4069 03:40:16,989 --> 03:40:18,724 INTELLECTUAL PROPERTY RIGHTS 4070 03:40:18,724 --> 03:40:19,959 BEING SOLVED INTO AN ACTUAL 4071 03:40:19,959 --> 03:40:22,662 THERAPY IF WE EVER GET THERE AND 4072 03:40:22,662 --> 03:40:27,333 IF WE'RE STRUGGLING I HEARD A 4073 03:40:27,333 --> 03:40:29,068 LOT IT'S DIFFICULT BUT I DON'T 4074 03:40:29,068 --> 03:40:30,770 HEAR ANY ACTUAL SOLUTIONS. 4075 03:40:30,770 --> 03:40:36,309 AND SO COULD YOU BE MORE 4076 03:40:36,309 --> 03:40:36,909 SPECIFIC AND I REALIZE 4077 03:40:36,909 --> 03:40:38,444 INTELLECTUAL PROPERTY RIGHTS ARE 4078 03:40:38,444 --> 03:40:39,545 DIFFICULT BUT THERE'S A LOT OF 4079 03:40:39,545 --> 03:40:42,448 PEOPLE THAT DEPEND ON US. 4080 03:40:42,448 --> 03:40:45,384 AND SO SPECIFICS I THINK ARE 4081 03:40:45,384 --> 03:40:45,651 IMPORTANT. 4082 03:40:45,651 --> 03:40:55,761 SO -- 4083 03:41:03,502 --> 03:41:06,238 >> IF THERE WAS A CURE TODAY 4084 03:41:06,238 --> 03:41:08,641 THAT HAD INTELLECTUAL PROPERTY 4085 03:41:08,641 --> 03:41:10,743 CONTRIBUTIONS FROM EACH OF US 4086 03:41:10,743 --> 03:41:13,579 HERE I EXPECT OUR RESPECTIVE 4087 03:41:13,579 --> 03:41:15,448 INSTITUTIONS WOULD BE ABLE TO 4088 03:41:15,448 --> 03:41:17,316 WORK THAT OUT. 4089 03:41:17,316 --> 03:41:19,852 AND SO I THINK I'LL START THERE 4090 03:41:19,852 --> 03:41:27,159 I DON'T THINK THAT'S THE HURDLE. 4091 03:41:27,159 --> 03:41:31,263 THE HURDLE IS WHERE THE 4092 03:41:31,263 --> 03:41:32,765 QUESTIONS THAT SWIRLED FROM THE 4093 03:41:32,765 --> 03:41:35,434 PREVIOUS DISCUSSION AND BEING 4094 03:41:35,434 --> 03:41:39,405 HIT HERE WHAT IS THE PATH? 4095 03:41:39,405 --> 03:41:41,474 SO THEN THE SOLUTIONS ARE 4096 03:41:41,474 --> 03:41:43,442 OBVIOUS ONES FOR THAT PATH TO 4097 03:41:43,442 --> 03:41:45,411 START THE DISCUSSION. 4098 03:41:45,411 --> 03:41:50,716 ANYONE ELSE WANT IT WEIGH IN? 4099 03:41:50,716 --> 03:41:53,853 >> I THINK IF THERE'S A SPECIFIC 4100 03:41:53,853 --> 03:41:54,920 COMBINATION AND EVIDENCE TO 4101 03:41:54,920 --> 03:41:55,554 SUPPORT IT AN AGREEMENT CAN BE 4102 03:41:55,554 --> 03:42:02,895 MADE. 4103 03:42:02,895 --> 03:42:10,703 MECHE AND GILL -- GILEAD ARE 4104 03:42:10,703 --> 03:42:14,306 BRINGING IT THROUGH AND WHEN 4105 03:42:14,306 --> 03:42:16,876 IT'S DIFFUSED AND THERE'S NOT 4106 03:42:16,876 --> 03:42:17,643 ENOUGH EVIDENCE TO SAY IT WILL 4107 03:42:17,643 --> 03:42:19,278 WORK OUTRIGHT IT'S HARD IT TAKE 4108 03:42:19,278 --> 03:42:20,112 THAT RISK. 4109 03:42:20,112 --> 03:42:23,382 SO IT'S ABOUT DE RISKING AND 4110 03:42:23,382 --> 03:42:25,384 PART OF THAT IS DOING THE 4111 03:42:25,384 --> 03:42:25,618 SCIENCE. 4112 03:42:25,618 --> 03:42:29,689 UNDERSTAND HADDING -- 4113 03:42:29,689 --> 03:42:32,224 UNDERSTANDING THE FUNDAMENTAL 4114 03:42:32,224 --> 03:42:33,693 BIOLOGY AND TAKING EACH ASSET 4115 03:42:33,693 --> 03:42:36,362 AND SHOWING WHAT IT CAN DO ON 4116 03:42:36,362 --> 03:42:39,432 ITS OWN AND THE COMBINATION A 4117 03:42:39,432 --> 03:42:47,473 GREATER PROBABILITY OF SUCCESS. 4118 03:42:47,473 --> 03:42:50,743 >> I AGREE AND MY FOLLOW-UP 4119 03:42:50,743 --> 03:42:53,112 QUESTION IS NDAs TAKE A LONG 4120 03:42:53,112 --> 03:42:59,985 TIME IS THERE A WAY TO SHORTEN 4121 03:42:59,985 --> 03:43:09,061 THE TIME AS A HURDLE TO GETTING 4122 03:43:09,061 --> 03:43:12,098 TRIALS DONE AND FOR OTHERS IT 4123 03:43:12,098 --> 03:43:22,408 COULD BE AN ISSUE. 4124 03:43:26,245 --> 03:43:29,782 I THINK IF THERE WAS AN 4125 03:43:29,782 --> 03:43:31,016 INTERMEDIATE ENTITY BETWEEN THE 4126 03:43:31,016 --> 03:43:34,420 NDCs AND PHARMA COMPANIES AND I 4127 03:43:34,420 --> 03:43:39,225 THINK ACTG DOES THIS WELL TO 4128 03:43:39,225 --> 03:43:43,362 INTERACT WITH A PARTNER FOR 4129 03:43:43,362 --> 03:43:45,664 DRUGS AVAILABLE IS PART OF THE 4130 03:43:45,664 --> 03:43:46,332 COMPLEXITY. 4131 03:43:46,332 --> 03:43:47,500 IT MAY IN THE JUST BE 4132 03:43:47,500 --> 03:43:52,438 INTERACTING WITH YOUR UNIVERSITY 4133 03:43:52,438 --> 03:44:02,982 BUT THOSE IN THE COLLABORATORY 4134 03:44:04,283 --> 03:44:10,089 IT QUAN CAN SLOW IT DOWN. 4135 03:44:10,089 --> 03:44:12,925 >> THEY SIT THERE AND IT'S BAND 4136 03:44:12,925 --> 03:44:19,431 WITH FOR THE PARTIES IN THE NTA. 4137 03:44:19,431 --> 03:44:20,533 SOMETIMES MERCK COMES BACK A 4138 03:44:20,533 --> 03:44:26,305 COUPLE DAYS AND WE'RE THERE FOR 4139 03:44:26,305 --> 03:44:28,774 WEEKS WE HAVE OTHER PRIORITIES 4140 03:44:28,774 --> 03:44:32,344 AND THE PEOPLE DOING NTAs ARE 4141 03:44:32,344 --> 03:44:39,585 BUSY AND TAKES WEEKS. 4142 03:44:39,585 --> 03:44:43,422 THE MORE COMPLEXITY THE LONGER 4143 03:44:43,422 --> 03:44:47,459 IT TAKES. 4144 03:44:47,459 --> 03:44:52,798 >> THERE'S A QUESTION FOR THE 4145 03:44:52,798 --> 03:44:53,766 OTHER PANELISTS. 4146 03:44:53,766 --> 03:44:56,535 YOU GUYS ARE READING ALL THE 4147 03:44:56,535 --> 03:44:58,437 GREAT WORK THESE FOLKS ARE DOING 4148 03:44:58,437 --> 03:45:00,472 AND YET IT SEEMS THERE'S A HUGE 4149 03:45:00,472 --> 03:45:02,641 AMOUNT OF PRECLINICAL ACTIVITY 4150 03:45:02,641 --> 03:45:04,043 THAT WOULD HAPPEN WITHIN YOUR 4151 03:45:04,043 --> 03:45:05,811 COMPANY THAT WOULD SORT OF TAKE 4152 03:45:05,811 --> 03:45:07,947 AN EXCITING FINDING AND A PAPER 4153 03:45:07,947 --> 03:45:09,982 AND GET IT TO A DERISK POINT 4154 03:45:09,982 --> 03:45:12,785 WHERE YOU MIGHT INVEST IN A 4155 03:45:12,785 --> 03:45:13,819 CLINICAL STUDY. 4156 03:45:13,819 --> 03:45:16,288 BRIDGING THAT GAP WAS A FOCUS 4157 03:45:16,288 --> 03:45:18,057 LAST DISCUSSION AND MIGHT BE 4158 03:45:18,057 --> 03:45:19,425 USEFUL IF THE INDUSTRY FOLKS CAN 4159 03:45:19,425 --> 03:45:22,027 TALK A LITTLE BIT WHAT THE 4160 03:45:22,027 --> 03:45:23,829 PROCESS LOOKS LIKE WHEN YOU READ 4161 03:45:23,829 --> 03:45:26,665 A PAPER WITH AN EXCITING NEW 4162 03:45:26,665 --> 03:45:31,904 TREATMENT MODALITY AND HAVE 4163 03:45:31,904 --> 03:45:33,839 ASSETS WHAT ARE STEPS BETWEEN 4164 03:45:33,839 --> 03:45:37,009 THE PAPER AND INITIATING THE 4165 03:45:37,009 --> 03:45:38,744 CLINICAL STUDIED AND IF FOLKS IN 4166 03:45:38,744 --> 03:45:39,812 THE ROOM CAN UNDERSTAND THAT 4167 03:45:39,812 --> 03:45:41,547 BETTER MAY BE ABLE TO MEET YOU 4168 03:45:41,547 --> 03:45:43,115 AT A LOWER RISK POINT. 4169 03:45:43,115 --> 03:45:45,784 >> I CAN GIVE A GOOD EXAMPLE HOW 4170 03:45:45,784 --> 03:45:49,288 THAT HAPPENED INSIDE THE 4171 03:45:49,288 --> 03:45:51,156 COLLABORATORY THINKING ABOUT THE 4172 03:45:51,156 --> 03:45:56,428 RESPECT OF MEMETICS. 4173 03:45:56,428 --> 03:46:02,368 WE SAW A GREAT PAPER THE IP 4174 03:46:02,368 --> 03:46:03,402 PROTEINS INVOLVED IN IP 4175 03:46:03,402 --> 03:46:06,338 EXPRESSION AND ANTAGONIZE THE 4176 03:46:06,338 --> 03:46:07,973 SMALL MOLECULES YOU CAN DRIVES 4177 03:46:07,973 --> 03:46:09,642 THE VIRUS OUT OF LATENCY. 4178 03:46:09,642 --> 03:46:12,611 IT LED TO A SERIES OF WHAT WE 4179 03:46:12,611 --> 03:46:14,580 CALL TARGET VALIDATION 4180 03:46:14,580 --> 03:46:15,414 EXPERIMENT. 4181 03:46:15,414 --> 03:46:18,617 THAT'S VALIDATE THE TARGET AND 4182 03:46:18,617 --> 03:46:21,220 AT THE SAME TIME START MAKING 4183 03:46:21,220 --> 03:46:23,756 SMALL MOLECULE ANALOGS TO SEE IF 4184 03:46:23,756 --> 03:46:27,459 THAT'S THE BEST ONE AND CAN FIND 4185 03:46:27,459 --> 03:46:29,194 MORE AND THE PROCESS OF 4186 03:46:29,194 --> 03:46:32,364 IDENTIFYING THE MOLECULE TO TAKE 4187 03:46:32,364 --> 03:46:33,599 THROUGH IN VITRO EXPERIMENTS, IN 4188 03:46:33,599 --> 03:46:39,238 VIVO EXPERIMENTS IN THE MOUSE 4189 03:46:39,238 --> 03:46:48,347 WITH THE PRIMATE WITH ANN AT 4190 03:46:48,347 --> 03:46:49,281 EMORY THAT PROCESS PROBABLY TOOK 4191 03:46:49,281 --> 03:46:51,884 FIVE YEARS START TO FINISH WITH 4192 03:46:51,884 --> 03:47:00,259 THE IN VITRO SIDE ONE WILL A 4193 03:47:00,259 --> 03:47:04,129 TEAM OF THAT ENDED UP IN THE 4194 03:47:04,129 --> 03:47:05,464 FIVE TO 10 PEOPLE RANGE. 4195 03:47:05,464 --> 03:47:07,232 I DON'T KNOW HOW MUCH WAS 4196 03:47:07,232 --> 03:47:09,935 INVESTED JUST TO GET TO THE 4197 03:47:09,935 --> 03:47:10,669 MOLECULE AND THEN THE 4198 03:47:10,669 --> 03:47:13,072 COLLABORATORY TO DO THE ANIMAL 4199 03:47:13,072 --> 03:47:14,073 MODEL STUDIES. 4200 03:47:14,073 --> 03:47:14,940 THERE'S A SUBSTANTIAL AMOUNT OF 4201 03:47:14,940 --> 03:47:25,651 INVESTMENT THAT LHAPPENS AND TH 4202 03:47:28,854 --> 03:47:30,990 TYPICAL APPROACH IS TO WAIT TO 4203 03:47:30,990 --> 03:47:36,295 PHASE II AND WE DESCRIBED THE 4204 03:47:36,295 --> 03:47:38,063 PROCESS IMMEDIATELY AFTER THE 4205 03:47:38,063 --> 03:47:39,798 ANIMAL STUDY SHOWED IT WORK AND 4206 03:47:39,798 --> 03:47:41,133 LET THE COMMUNITY SEE THE TARGET 4207 03:47:41,133 --> 03:47:42,267 AND DEVELOPED THE TARGET BECAUSE 4208 03:47:42,267 --> 03:47:44,436 IT WAS DONE AS PART OF THE 4209 03:47:44,436 --> 03:47:45,471 COLLABORATORY. 4210 03:47:45,471 --> 03:47:48,107 THAT'S A PRETTY GOOD EXAMPLE HOW 4211 03:47:48,107 --> 03:47:53,078 THAT CAN HAPPEN IN THIS 4212 03:47:53,078 --> 03:47:54,146 COLLABORATIVE SETTING. 4213 03:47:54,146 --> 03:47:55,414 MAYBE OTHERS WOULD DRAW 4214 03:47:55,414 --> 03:48:05,891 ATTENTION TO OTHER EXAMPLES. 4215 03:48:08,427 --> 03:48:10,596 >> THERE'S TARGET VALIDATIONS 4216 03:48:10,596 --> 03:48:12,364 WITHIN OUR OWN ASSAY AND MODELS 4217 03:48:12,364 --> 03:48:15,067 IN HOUSE IS THE FIRST STEP. 4218 03:48:15,067 --> 03:48:16,201 PUBLICATIONS ARE GREAT BUT WE 4219 03:48:16,201 --> 03:48:19,371 NEED TO BE ABLE TO RECAPITULATE 4220 03:48:19,371 --> 03:48:19,872 AND FOLLOW-UP WITH OUR 4221 03:48:19,872 --> 03:48:23,075 PARAMETERS. 4222 03:48:23,075 --> 03:48:24,276 THAT'S A KEY FIRST STEP AND THAT 4223 03:48:24,276 --> 03:48:29,381 CAN TAKE A WHILE. 4224 03:48:29,381 --> 03:48:34,453 AND COULD BE A BETTER TOOL 4225 03:48:34,453 --> 03:48:35,654 MOLECULE TO RECAPITULATE THOSE 4226 03:48:35,654 --> 03:48:45,798 RESULTS. 4227 03:48:48,567 --> 03:48:50,402 >> I WANTED TO SHIFT GEARS A 4228 03:48:50,402 --> 03:48:52,171 LITTLE BIT. 4229 03:48:52,171 --> 03:48:54,206 I'M A PROGRAM OFFICER AT DADE. 4230 03:48:54,206 --> 03:48:57,910 I'M INVOLVED IN BEAT HIV AND 4231 03:48:57,910 --> 03:48:59,711 HOPE AND IN MY ROLE I HAVE THE 4232 03:48:59,711 --> 03:49:02,247 PRIVILEGE OF WORKING WITH ALL 4233 03:49:02,247 --> 03:49:03,315 OUR COMMUNITY REPRESENTATIVES 4234 03:49:03,315 --> 03:49:06,718 AND GET THEIR FEEDBACK ALL THE 4235 03:49:06,718 --> 03:49:06,919 TIME. 4236 03:49:06,919 --> 03:49:07,786 I'VE HEARD A LOT WHEN THEY'RE 4237 03:49:07,786 --> 03:49:10,322 GOING OUT IN THE PUBLIC TRYING 4238 03:49:10,322 --> 03:49:12,991 TO EDUCATE THE PUBLIC ABOUT HIV 4239 03:49:12,991 --> 03:49:13,192 CURE. 4240 03:49:13,192 --> 03:49:15,928 THEY HEAR BACK A LOT BIG PHARMA 4241 03:49:15,928 --> 03:49:18,430 DOESN'T WANT TO CURE HIV BECAUSE 4242 03:49:18,430 --> 03:49:19,932 THAT MAKE SO MUCH OFF OUR DRUG 4243 03:49:19,932 --> 03:49:20,933 AND SO FORTH. 4244 03:49:20,933 --> 03:49:21,667 . 4245 03:49:21,667 --> 03:49:22,734 AND I KNOW IT'S MISINFORMATION 4246 03:49:22,734 --> 03:49:24,636 BUT IT'S DIFFICULT TO CONVINCE 4247 03:49:24,636 --> 03:49:25,471 SOMEBODY ELSE AND I'M SURE YOU 4248 03:49:25,471 --> 03:49:27,573 HEAR THIS ALL THE TIME. 4249 03:49:27,573 --> 03:49:33,278 ARE THERE TALKING POINTS FOR THE 4250 03:49:33,278 --> 03:49:34,346 COMMUNITY REPS TO HELP THEM GET 4251 03:49:34,346 --> 03:49:44,523 PAST THAT? 4252 03:49:47,359 --> 03:49:49,061 >> WE DO OUTREACH AND THE 4253 03:49:49,061 --> 03:49:52,431 CYNICAL POSITION IS ONE PRETTY 4254 03:49:52,431 --> 03:49:55,000 WELL ESTABLISHED AND HARD ONE TO 4255 03:49:55,000 --> 03:49:56,735 BEAT EVEN IF WE WERE OUT FULL 4256 03:49:56,735 --> 03:49:59,071 TIME TALKING WITH THE BEST 4257 03:49:59,071 --> 03:50:04,209 TALKING POINTS I THINK WE'D HAVE 4258 03:50:04,209 --> 03:50:05,744 A SUBSTANTIAL POPULATION THAT 4259 03:50:05,744 --> 03:50:14,386 BELIEVES AND THE COMMUNITY 4260 03:50:14,386 --> 03:50:18,524 ADVISORY BOARD AND THEN OUR OWN 4261 03:50:18,524 --> 03:50:19,458 COMMUNITY ENGAGEMENT PROCESSES 4262 03:50:19,458 --> 03:50:23,428 ARE KEY TO THAT AS WELL. 4263 03:50:23,428 --> 03:50:33,639 ANYONE ELSE? 4264 03:50:41,446 --> 03:50:46,885 >> WHEN YOU TALK TO THE 4265 03:50:46,885 --> 03:50:51,423 COMMUNITY IT'S IMPORTANT TO 4266 03:50:51,423 --> 03:50:55,994 UNDERSTAND THERE'S COMPANIES 4267 03:50:55,994 --> 03:50:57,262 WITH ANTIRETROVIRALS AND TO SAY 4268 03:50:57,262 --> 03:50:58,564 THEY DON'T WANT A CURE BECAUSE 4269 03:50:58,564 --> 03:50:59,665 THEY WANT TO CONTINUE TO SELL 4270 03:50:59,665 --> 03:51:04,336 THEIR DRUGS IS MISINFORMATION. 4271 03:51:04,336 --> 03:51:09,741 AND POINTING TO THE FACT THAT 4272 03:51:09,741 --> 03:51:11,076 GILEAD IS INVOLVED IN SEVERAL 4273 03:51:11,076 --> 03:51:14,213 TRIALS WITH THE TRL9 AGONIST AND 4274 03:51:14,213 --> 03:51:16,415 OTHER COMPOUNDS SPEAKS TO THE 4275 03:51:16,415 --> 03:51:21,053 FACT THAT, YES, CURE IS STILL 4276 03:51:21,053 --> 03:51:26,258 STRONG POINT OF PURPOSE. 4277 03:51:26,258 --> 03:51:26,425 4278 03:51:26,425 --> 03:51:29,428 >> TO ADD TO THAT I THINK 4279 03:51:29,428 --> 03:51:31,063 LOOKING AT HOW BIG THE PORTFOLIO 4280 03:51:31,063 --> 03:51:32,564 IS NOT ONLY AT SINGLE COMPANIES 4281 03:51:32,564 --> 03:51:37,869 BUT ACROSS THE COMPANIES I THINK 4282 03:51:37,869 --> 03:51:42,574 AT GILEAD WE HAVE SEVERAL SAETS 4283 03:51:42,574 --> 03:51:45,577 IN THE PIPELINE AND I THINK IT'S 4284 03:51:45,577 --> 03:51:47,980 A SIGN WE'RE COMMITTED TO IT AND 4285 03:51:47,980 --> 03:51:49,581 ARE DOING ACHT COMMUNITY 4286 03:51:49,581 --> 03:51:51,450 ENGAGEMENT TO TRY TO GET THAT 4287 03:51:51,450 --> 03:51:53,385 MESSAGE OUT. 4288 03:51:53,385 --> 03:51:58,991 WE HAVE AN HIV CURE DEDICATED 4289 03:51:58,991 --> 03:51:59,992 COMMUNITY ADVISORY BOARD WE'RE 4290 03:51:59,992 --> 03:52:02,160 HOPING WILL CONTINUE TO SPREAD 4291 03:52:02,160 --> 03:52:04,129 THE MESSAGE AND INVESTED NOT 4292 03:52:04,129 --> 03:52:09,534 ONLY IN OUR OWN INTERNAL EFFORTS 4293 03:52:09,534 --> 03:52:14,473 AND WE HAD A WHOLE HIV CURE 4294 03:52:14,473 --> 03:52:17,576 GRANT PROGRAM THAT WAS GEARED 4295 03:52:17,576 --> 03:52:19,811 TOWARDS FUNDING NOVEL IDEAS WITH 4296 03:52:19,811 --> 03:52:22,848 THE IDEA OF BRINGING NEW IDEAS 4297 03:52:22,848 --> 03:52:30,389 AND POTENTIAL PRODUCTS INTO THE 4298 03:52:30,389 --> 03:52:30,656 PIPELINE. 4299 03:52:30,656 --> 03:52:33,925 AND FOR EVERYONE IN THE FIELD. 4300 03:52:33,925 --> 03:52:38,430 >> I ECHO EVERYTHING SAID AND 4301 03:52:38,430 --> 03:52:43,435 SAY WE'VE DONE IT BEFORE. 4302 03:52:43,435 --> 03:52:46,171 AND WE HAD THERAPIES NOT SO 4303 03:52:46,171 --> 03:52:49,441 GREAT AND LOW CURE RATES. 4304 03:52:49,441 --> 03:52:55,414 WE MOVED ON AND DID THE FIRST 4305 03:52:55,414 --> 03:52:56,948 PROTEASE INHIBITORS AND 4306 03:52:56,948 --> 03:52:59,685 ULTIMATELY GOT A TWO-DRUG 4307 03:52:59,685 --> 03:53:02,087 REGIMENT OVER WEEKS. 4308 03:53:02,087 --> 03:53:06,124 IT'S A STEPWISE PROFESSION AND 4309 03:53:06,124 --> 03:53:11,963 LOOK WHAT WE DID WITH HCV. 4310 03:53:11,963 --> 03:53:18,437 WHERE HE STARTED WITH LARGE 4311 03:53:18,437 --> 03:53:20,605 SINGLE PILL REGIMENTS AND WILL 4312 03:53:20,605 --> 03:53:21,673 HOPEFULLY HAVE LONG ACTING AND 4313 03:53:21,673 --> 03:53:23,775 THE NEXT STEP IS CURE. 4314 03:53:23,775 --> 03:53:25,043 THIS IS THE NATURAL PATH AND 4315 03:53:25,043 --> 03:53:26,445 WHAT WE'VE DONE AND WHAT WE'LL 4316 03:53:26,445 --> 03:53:36,722 CONTINUE TO DO. 4317 03:53:37,155 --> 03:53:39,391 >> WE TALK ABOUT THE ADVISORY 4318 03:53:39,391 --> 03:53:44,896 BOARDS OF INCENTIVIZING BETTER 4319 03:53:44,896 --> 03:53:46,064 RELATIONSHIPS ONE THE INDUSTRY 4320 03:53:46,064 --> 03:53:47,432 AND REACH OUT AND SAY WOULD YOU 4321 03:53:47,432 --> 03:53:48,867 BE WILLING TO PARTNER WITH A 4322 03:53:48,867 --> 03:53:53,171 PARTICULAR PROGRAM BECAUSE YOU 4323 03:53:53,171 --> 03:53:56,641 HAVE A GREAT ASSET AND WE GET 4324 03:53:56,641 --> 03:53:58,377 THE LETTER AND GRANT AND DO THE 4325 03:53:58,377 --> 03:54:08,487 WORK ANDO -- OR THE MECHANISM 4326 03:54:08,487 --> 03:54:10,155 OF SUPPORT AND A GRANT FROM NIH 4327 03:54:10,155 --> 03:54:13,158 SUPPORT AND ACADEMIC EFFORTS AT 4328 03:54:13,158 --> 03:54:15,594 A SUBSIDIZED RATE AND THAT'S 4329 03:54:15,594 --> 03:54:16,595 WONDERFUL AS WELL. 4330 03:54:16,595 --> 03:54:21,833 MY QUESTION IS WHAT OTHER MODELS 4331 03:54:21,833 --> 03:54:28,039 CAN WE THINK ABOUT? 4332 03:54:28,039 --> 03:54:30,342 WOULD IT BE HELP SUPPORT THE 4333 03:54:30,342 --> 03:54:32,411 VALE OF DEATH WITH ACADEMIA AND 4334 03:54:32,411 --> 03:54:33,645 INDUSTRY AND WOULD YOU BE ABLE 4335 03:54:33,645 --> 03:54:36,481 TO TAP YOUR RESOURCES IN SUPPORT 4336 03:54:36,481 --> 03:54:38,383 OF ACADEMIA IF THERE WERE 4337 03:54:38,383 --> 03:54:39,885 INSTRUMENTS THAT WOULD JOINTLY 4338 03:54:39,885 --> 03:54:41,586 GIVE YOU MONEY BECAUSE NORMALLY 4339 03:54:41,586 --> 03:54:43,355 WE DON'T PUT MONEY IN THE GRANTS 4340 03:54:43,355 --> 03:54:45,991 AND WE EXPECT YOU TO FLIP THE 4341 03:54:45,991 --> 03:54:48,760 BILL AND GET US A LETTER. 4342 03:54:48,760 --> 03:54:49,694 WITH REGARDS TO THE FUTURE IS 4343 03:54:49,694 --> 03:54:50,695 THERE ANOTHER WAY TO THINK ABOUT 4344 03:54:50,695 --> 03:54:56,601 OUR PARTNERSHIPS THAT PERHAPS 4345 03:54:56,601 --> 03:55:07,112 FROM YOUR SIDE OR IS THIS THE 4346 03:55:15,487 --> 03:55:17,522 BEST WE CAN DO 4347 03:55:17,522 --> 03:55:21,927 >> CAN EVERYONE HEAR ME? 4348 03:55:21,927 --> 03:55:23,428 >> YES. 4349 03:55:23,428 --> 03:55:25,330 >> I'VE HAD EXPERIENCE WITH TWO 4350 03:55:25,330 --> 03:55:27,899 CLINICAL TRIAL AND TWO OF WHICH 4351 03:55:27,899 --> 03:55:31,102 I'VE BEEN ON THE PROTOCOL TEAM 4352 03:55:31,102 --> 03:55:31,369 FOR. 4353 03:55:31,369 --> 03:55:32,671 I'LL MENTION THE NAME OF THE 4354 03:55:32,671 --> 03:55:33,472 PHARMACEUTICAL COMPANY SINCE 4355 03:55:33,472 --> 03:55:44,015 IT'S ALREADY BEEN MENTIONED, BMS 4356 03:55:44,516 --> 03:55:48,253 WE HAD AN HIV DIVISION AND THEY 4357 03:55:48,253 --> 03:55:51,423 ENDED THAT AS PEOPLE ARE 4358 03:55:51,423 --> 03:55:56,962 PROBABLY AWARE AND NOW WHEN A 4359 03:55:56,962 --> 03:56:02,567 PROTOCOL REACHES OUT FOR A 4360 03:56:02,567 --> 03:56:04,603 COMPOUND FOR AN HIV TRIAL THEY 4361 03:56:04,603 --> 03:56:06,972 WANT NOTHING TO DO WITH IT. 4362 03:56:06,972 --> 03:56:11,309 THE CRITICISM THAT EXISTS 4363 03:56:11,309 --> 03:56:12,878 LARGELY IS WITH COMPANIES THAT 4364 03:56:12,878 --> 03:56:14,813 ARE NO LONGER IN THE HIV SPACE 4365 03:56:14,813 --> 03:56:16,147 OR ARE NOT IN THE HIV SPACE. 4366 03:56:16,147 --> 03:56:22,120 WE'RE NOT TALKING ABOUT MERCK 4367 03:56:22,120 --> 03:56:23,889 AND VIIV AND GILEAD. 4368 03:56:23,889 --> 03:56:34,366 YOU ALL DO VERY WELL FOR US. 4369 03:56:36,101 --> 03:56:37,402 WHEN YOU HAVE A COMPOUND 4370 03:56:37,402 --> 03:56:38,203 APPRESSED FOR ONE INDICATION AND 4371 03:56:38,203 --> 03:56:44,643 THEN WANT TO USE IT FOR HIV, AND 4372 03:56:44,643 --> 03:56:50,348 THERE'S A FEAR THAT THE TRIAL 4373 03:56:50,348 --> 03:56:53,084 COULD POTENTIALLY HAVE A 4374 03:56:53,084 --> 03:56:54,219 NEGATIVE OUTCOME AND POTENTIALLY 4375 03:56:54,219 --> 03:56:59,457 GET THAT DRUG PULLED FROM THE 4376 03:56:59,457 --> 03:57:03,795 MARKET WELL, IF THAT'S THE FEAR 4377 03:57:03,795 --> 03:57:05,230 YOU NEED TO DO SOMETHING ABOUT 4378 03:57:05,230 --> 03:57:06,965 THE FEAR. 4379 03:57:06,965 --> 03:57:08,733 THE SOLUTION WOULD BE TO NOT 4380 03:57:08,733 --> 03:57:11,803 TRASH ONE DRUG BECAUSE IT DIDN'T 4381 03:57:11,803 --> 03:57:13,405 WORK FOR A CERTAIN INDICATION 4382 03:57:13,405 --> 03:57:18,510 AND IT DOES FOR ANOTHER 4383 03:57:18,510 --> 03:57:18,810 INDICATION. 4384 03:57:18,810 --> 03:57:26,585 I KNOW AND CERTAIN DRUGS YOU 4385 03:57:26,585 --> 03:57:28,386 CAN'T GIVE TO CERTAIN PEOPLE BUT 4386 03:57:28,386 --> 03:57:30,322 FINE FOR WHAT THEY'RE APPROVED 4387 03:57:30,322 --> 03:57:33,525 FOR. 4388 03:57:33,525 --> 03:57:35,827 WHEN IT BECOMES UNAFFORDABLE TO 4389 03:57:35,827 --> 03:57:36,861 REPURPOSE OR USING A DRUG AND 4390 03:57:36,861 --> 03:57:42,233 THEN THEY ARE HAVE TO SCRAMBLE 4391 03:57:42,233 --> 03:57:45,537 AND CHANGE THE PROTOCOL AND LOOK 4392 03:57:45,537 --> 03:57:47,405 FOR A DIFFERENT COMPOUND, IT 4393 03:57:47,405 --> 03:57:49,541 JUST COST MORE MONEY AND TAKES 4394 03:57:49,541 --> 03:57:50,375 MORE TIME. 4395 03:57:50,375 --> 03:58:00,752 IF WE CAN INCENTIVIZE 4396 03:58:03,288 --> 03:58:05,690 PHARMACEUTICAL COMPANIES TO PLAY 4397 03:58:05,690 --> 03:58:07,626 NICELY AND SOME HELP WOULD BE 4398 03:58:07,626 --> 03:58:08,927 REALLY NICE. 4399 03:58:08,927 --> 03:58:11,262 IF THERE COULD BE AN INCENTIVE 4400 03:58:11,262 --> 03:58:13,231 FROM THE FDA OR OTHERWISE, I 4401 03:58:13,231 --> 03:58:18,536 THINK THAT WOULD GO A LONG WAY 4402 03:58:18,536 --> 03:58:19,471 TO GETTING US FURTHER DOWN THE 4403 03:58:19,471 --> 03:58:22,874 ROAD WHERE WE NEED TO BE FOR A 4404 03:58:22,874 --> 03:58:23,742 CURE AND OTHER THINGS. 4405 03:58:23,742 --> 03:58:29,014 >> THANK YOU FOR COMMENTING. 4406 03:58:29,014 --> 03:58:34,486 AND RELATE D ALL THIS COMES TO 4407 03:58:34,486 --> 03:58:36,855 RISK ASSET CALCULATION DONE BY 4408 03:58:36,855 --> 03:58:42,027 MULTIPLE PEOPLE WITHIN EACH 4409 03:58:42,027 --> 03:58:42,327 INSTITUTION. 4410 03:58:42,327 --> 03:58:46,831 AND IF WE CAN FIND WAYS TO TWEAK 4411 03:58:46,831 --> 03:58:53,571 THAT AND DECREASE RISK VIA 4412 03:58:53,571 --> 03:58:55,740 SAFETY RISK AROUND REPURPOSING 4413 03:58:55,740 --> 03:58:59,310 FOR INTELLECTUAL PROPERTY RISK 4414 03:58:59,310 --> 03:59:03,915 FOR THE NOVEL COMPOUNDING IN 4415 03:59:03,915 --> 03:59:04,582 COMBINATION WITH OTHER 4416 03:59:04,582 --> 03:59:07,452 INSTITUTIONS THAT'S HOW WE'RE 4417 03:59:07,452 --> 03:59:09,954 GOING TO DO THIS. 4418 03:59:09,954 --> 03:59:11,589 IF WE CAN DECREASE THE RISK OR 4419 03:59:11,589 --> 03:59:17,495 BENEFIT WE CAN MOVE FORWARD. 4420 03:59:17,495 --> 03:59:19,431 >> NOBODY WOULD TURN DOWN THE 4421 03:59:19,431 --> 03:59:20,365 NOBEL PRIZE FOR CURING HIV, 4422 03:59:20,365 --> 03:59:20,765 TRUST ME. 4423 03:59:20,765 --> 03:59:26,337 >> I DON'T HAVE A SUGGESTION FOR 4424 03:59:26,337 --> 03:59:29,307 HOW TO DO THAT BUT MAYBE 4425 03:59:29,307 --> 03:59:30,809 PANELISTS DO AND MAYBE THE 4426 03:59:30,809 --> 03:59:33,411 AUDIENCE DOES AND MAYBE USE THE 4427 03:59:33,411 --> 03:59:35,346 REST OF THE TIME AS THE LAST 4428 03:59:35,346 --> 03:59:37,582 GROUP DID GO TO A SOLUTION. 4429 03:59:37,582 --> 03:59:41,986 >> I WANTED TO SPEAK TO 4430 03:59:41,986 --> 03:59:44,089 SOMETHING LOUIS SAID. 4431 03:59:44,089 --> 03:59:46,858 OUR BIGGEST COST DON'T COME AT 4432 03:59:46,858 --> 03:59:48,226 THE DISCOVERY SPACE BUT THE 4433 03:59:48,226 --> 03:59:49,394 CLINICAL DEVELOPMENT SPACE. 4434 03:59:49,394 --> 03:59:53,465 IF YOUR WRITING GRANTS AND WANT 4435 03:59:53,465 --> 03:59:55,333 TO DEVELOP IT WITH THE INDUSTRY 4436 03:59:55,333 --> 03:59:58,837 PARTNER I DO THINK INCENTIVIZING 4437 03:59:58,837 --> 04:00:01,439 THAT WITH FUNDING WOULD BE 4438 04:00:01,439 --> 04:00:03,108 HELPFUL BECAUSE IF WE HAVE A 4439 04:00:03,108 --> 04:00:06,077 LARGE PORTFOLIO OF ASSETS AND 4440 04:00:06,077 --> 04:00:09,714 HAVE TO PRIORITIZE WHAT WE PULL 4441 04:00:09,714 --> 04:00:11,049 OUR INVESTMENT BEHIND SOMETHING 4442 04:00:11,049 --> 04:00:13,752 THAT IS A DON'T OF AN ALTERNATE 4443 04:00:13,752 --> 04:00:17,288 THERAPY IS GOING TO LOOK A 4444 04:00:17,288 --> 04:00:20,725 LOT -- WILL HAVE LOWER PRIORITY 4445 04:00:20,725 --> 04:00:23,995 OF A THERAPY IN AND OF ITSELF 4446 04:00:23,995 --> 04:00:25,330 AND CAN WRITE GRANTS FOR AN 4447 04:00:25,330 --> 04:00:26,498 INDUSTRY PARTNER AND PROVIDE 4448 04:00:26,498 --> 04:00:28,600 FUNDING FOR A CLINICAL 4449 04:00:28,600 --> 04:00:32,203 DEVELOPMENT I THINK YOU COULD 4450 04:00:32,203 --> 04:00:34,038 GET TRACTION AND MOVING ASSETS 4451 04:00:34,038 --> 04:00:35,607 THAT MAY NOT BE ON TOP OF THE 4452 04:00:35,607 --> 04:00:45,850 PRIORITY LIST. 4453 04:00:46,251 --> 04:00:49,854 >> IMMUNITY BIO IS AN ONCOLOGY 4454 04:00:49,854 --> 04:00:54,192 COMPANY AN 803 NOW CALL ANTIVA 4455 04:00:54,192 --> 04:00:58,029 WAS JUST APPROVED BACK IN APRIL 4456 04:00:58,029 --> 04:01:01,166 FOR USE IN BLADDER CANCER FROM 4457 04:01:01,166 --> 04:01:02,200 THE FDA. 4458 04:01:02,200 --> 04:01:05,603 IT ALSO MADE IT CHALLENGING TO 4459 04:01:05,603 --> 04:01:08,573 PROVIDE -- AND THIS IS ONE WITH 4460 04:01:08,573 --> 04:01:11,543 WHAT WAS TALKED ABOUT THIS 4461 04:01:11,543 --> 04:01:13,778 MORNING MENTIONING A PROBLEM 4462 04:01:13,778 --> 04:01:14,746 WITHIN 803. 4463 04:01:14,746 --> 04:01:20,018 IT WASN'T A PROBLEM BUT THE FACT 4464 04:01:20,018 --> 04:01:23,488 THAT AS RICK MENTIONED WAS RISK 4465 04:01:23,488 --> 04:01:25,757 BENEFIT DECISIONS BEING MADE IN 4466 04:01:25,757 --> 04:01:27,859 THE COMPANY SAYING WELL WE'RE 4467 04:01:27,859 --> 04:01:29,928 WAITING FOR THE FDA APPROVAL AT 4468 04:01:29,928 --> 04:01:32,764 THE MOMENT IF WE HAVE AN ADVERSE 4469 04:01:32,764 --> 04:01:39,204 EVENT IN A PRE CLINICAL STUDY 4470 04:01:39,204 --> 04:01:41,239 OUT COULD DERAIL THE PROGRAM AND 4471 04:01:41,239 --> 04:01:43,107 NO WAY THE COMPANY WILL ALLOW ME 4472 04:01:43,107 --> 04:01:46,911 TO PROVIDE THE DRUG IN THAT 4473 04:01:46,911 --> 04:01:47,312 SITUATION. 4474 04:01:47,312 --> 04:01:49,013 WE'RE PAST THAT SO HOPING IT 4475 04:01:49,013 --> 04:01:55,820 WILL BE EASIER BUT TO LUIS' 4476 04:01:55,820 --> 04:01:58,056 POINT IF THERE'S WAY TO GET 4477 04:01:58,056 --> 04:02:04,262 FUNDING FOR PROVIDING 803 OR 4478 04:02:04,262 --> 04:02:05,063 ANTIVA FOR ANY PART OF THE 4479 04:02:05,063 --> 04:02:06,931 PROCESS I WOULD WELCOME THAT AND 4480 04:02:06,931 --> 04:02:09,868 SO WOULD THE COMPANY. 4481 04:02:09,868 --> 04:02:11,970 RIGHT NOW IN EVERY SITUATION 4482 04:02:11,970 --> 04:02:13,171 WE'VE BEEN INVOLVED IN WITH 4483 04:02:13,171 --> 04:02:14,973 RESPECT TO EARLY PRE CLINICAL 4484 04:02:14,973 --> 04:02:19,210 WORK AND NOW IN CLINICAL 4485 04:02:19,210 --> 04:02:20,712 STUDIES, WE'VE GIVEN DRUG -- 4486 04:02:20,712 --> 04:02:23,615 THERE'S A COST TO DOING THAT 4487 04:02:23,615 --> 04:02:33,558 OBVIOUSLY. 4488 04:02:33,558 --> 04:02:36,361 AND MAKE SURE THERE'S A FUNDING 4489 04:02:36,361 --> 04:02:38,763 MECHANISM THAT REWARDED BOTH 4490 04:02:38,763 --> 04:02:39,898 PARTNERS IN THAT SITUATION. 4491 04:02:39,898 --> 04:02:42,934 >> ONE THING I'D LIKE TO ADD IS 4492 04:02:42,934 --> 04:02:45,570 SOMETIMES LIKE THE DERISKING 4493 04:02:45,570 --> 04:02:49,040 PROCESS WE TALKED ABOUT CAN ALSO 4494 04:02:49,040 --> 04:02:51,142 BE PART OF THE COLLABORATION. 4495 04:02:51,142 --> 04:02:56,781 FOR EXAMPLE, THERE'S THE ABILITY 4496 04:02:56,781 --> 04:02:58,950 TO WEIGH IN SOME SCIENTIFIC 4497 04:02:58,950 --> 04:03:00,385 ADVISER FROM THE COMPANY OR 4498 04:03:00,385 --> 04:03:01,953 ENTITY THAT PROVIDE THE DRUG, 4499 04:03:01,953 --> 04:03:03,421 THAT MAY HELP US MAYBE DESIGN 4500 04:03:03,421 --> 04:03:08,826 THE STUDY IN A WAY THAT IS LESS 4501 04:03:08,826 --> 04:03:11,930 RISKY FROM A SAFETY PERSPECTIVE, 4502 04:03:11,930 --> 04:03:17,302 FOR INSTANCE, SO THAT RISK 4503 04:03:17,302 --> 04:03:19,003 BENEFIT SCALE MOVE TOWARDS THE 4504 04:03:19,003 --> 04:03:19,604 BENEFIT AND LESS TOWARDS THE 4505 04:03:19,604 --> 04:03:29,314 RISK. 4506 04:03:29,314 --> 04:03:35,320 >> I'M A CO-CHAIR FOR HOPE AND 4507 04:03:35,320 --> 04:03:36,888 THANK YOU FOR BRINGING UP THE 4508 04:03:36,888 --> 04:03:38,690 TOPIC OF HIV CURE. 4509 04:03:38,690 --> 04:03:44,862 I WANTED TO ADD A TALKING POINT 4510 04:03:44,862 --> 04:03:47,165 AND FRAMING IT IN THAT COMPANIES 4511 04:03:47,165 --> 04:03:48,199 ARE DRIVEN BY PROFIT. 4512 04:03:48,199 --> 04:03:50,868 I'LL THROW THAT BACK AND SAY 4513 04:03:50,868 --> 04:03:52,337 THEN IT'S IN THE INTEREST OF A 4514 04:03:52,337 --> 04:03:54,872 COMPANY TO PURSUE CURE AND TO BE 4515 04:03:54,872 --> 04:03:56,541 THE FIRST TO COME TO MARKET WITH 4516 04:03:56,541 --> 04:03:57,875 A CURE. 4517 04:03:57,875 --> 04:03:59,911 IMAGINE THE RISK OF NOT PURSUING 4518 04:03:59,911 --> 04:04:01,579 CURE AND SITTING ON THE 4519 04:04:01,579 --> 04:04:02,080 SIDELINES AND LETTING 4520 04:04:02,080 --> 04:04:03,214 COMPETITORS GET ALL THE MONEY. 4521 04:04:03,214 --> 04:04:13,624 JUST WANTED TO ADD THAT. 4522 04:04:24,836 --> 04:04:26,838 >> THANK YOU FOR THE PANEL AND 4523 04:04:26,838 --> 04:04:28,873 I'VE ENJOYED THE DISCUSSION. 4524 04:04:28,873 --> 04:04:30,241 >> THANKS FOR EVERYONE STAYING 4525 04:04:30,241 --> 04:04:32,343 TO THE END AND FOR THE 4526 04:04:32,343 --> 04:04:33,511 OPPORTUNITY TO DISCUSS THIS. 4527 04:04:33,511 --> 04:04:37,081 I THINK I SPEAK FOR ALL OF US 4528 04:04:37,081 --> 04:04:42,286 WE'RE EXCITED ABOUT THE END 4529 04:04:42,286 --> 04:04:43,554 GROUND AND MAYBE WE CAN FIND A 4530 04:04:43,554 --> 04:04:44,589 WAY TO SOLVE SOME OF THE 4531 04:04:44,589 --> 04:04:54,132 PATTERNS. 4532 04:04:54,132 --> 04:04:56,868 >> WE'VE COME TO THE END OF THE 4533 04:04:56,868 --> 04:04:57,702 THREE-DAY EVENT. 4534 04:04:57,702 --> 04:05:02,874 I JUST WANT TO THANK OUR 4535 04:05:02,874 --> 04:05:11,449 LEADERSHIP STARTING OFF THE 4536 04:05:11,449 --> 04:05:12,850 NIAID DIRECTOR AND CARL AND 4537 04:05:12,850 --> 04:05:14,419 GUIDING US THROUGH THE PROCESS 4538 04:05:14,419 --> 04:05:17,655 AND THE PROGRAM MANAGEMENT TEAM 4539 04:05:17,655 --> 04:05:22,093 AND PROGRAM OFFICERS WHO HAVE 4540 04:05:22,093 --> 04:05:27,932 BEEN WONDERFUL IN MAKING THIS A 4541 04:05:27,932 --> 04:05:29,367 SUCCESSFUL GET TOGETHER AND 4542 04:05:29,367 --> 04:05:34,205 BESIDES NIAID WE HAVE OTHER ICOs 4543 04:05:34,205 --> 04:05:36,774 THAT SUPPORT THE MARTIN DELANEY 4544 04:05:36,774 --> 04:05:38,976 AND SPECIAL THANKS TO THE 4545 04:05:38,976 --> 04:05:39,410 INVESTIGATORS. 4546 04:05:39,410 --> 04:05:40,778 WITHOUT YOU WE'RE NOT HERE SO WE 4547 04:05:40,778 --> 04:05:44,215 THANK YOU FOR ALL THIS WONDERFUL 4548 04:05:44,215 --> 04:05:45,516 SCIENTIFIC DELIBERATIONS THE 4549 04:05:45,516 --> 04:05:45,917 LAST THREE DAYS. 4550 04:05:45,917 --> 04:05:53,191 WE APPRECIATE WHAT YOU DO. 4551 04:05:53,191 --> 04:05:54,792 FINALLY GET THIS THING DONE BUT 4552 04:05:54,792 --> 04:05:59,230 I APPRECIATE THE P.I.s FOR 4553 04:05:59,230 --> 04:06:00,198 SPONSORING AND CONTRIBUTING FOR 4554 04:06:00,198 --> 04:06:03,201 THE COUGH YO BREAKS AND THE NIH 4555 04:06:03,201 --> 04:06:04,469 PROGRAM OFFICER COLLEAGUES 4556 04:06:04,469 --> 04:06:06,070 BRINGING THE SNACKS. 4557 04:06:06,070 --> 04:06:07,271 WE APPRECIATE THAT AND NIH 4558 04:06:07,271 --> 04:06:08,873 STAFF. 4559 04:06:08,873 --> 04:06:12,477 IT'S BEEN A FANTASTIC MEETING 4560 04:06:12,477 --> 04:06:16,214 AND EVERY ONE OF YOU FOR MAKING 4561 04:06:16,214 --> 04:06:17,915 A SEAMLESS TRANSITION BETWEEN 4562 04:06:17,915 --> 04:06:18,249 PRESENTATIONS. 4563 04:06:18,249 --> 04:06:21,185 I PRESENT THAT AND THE NIH 4564 04:06:21,185 --> 04:06:26,524 VIDEOCAST WHO ARE STREAMING THIS 4565 04:06:26,524 --> 04:06:32,163 ONLINE WORLDWIDE AND WE ARE 4566 04:06:32,163 --> 04:06:33,898 CONTRACTOR SUPPORT AND WE WANT 4567 04:06:33,898 --> 04:06:36,868 TO THANK EVERYONE AND THANKS A 4568 04:06:36,868 --> 04:06:38,936 LOT AND WISH YOU A SAFE TRAVEL 4569 04:06:38,936 --> 04:06:39,504 BACK HOME. 4570 04:06:39,504 --> 04:06:39,904 SEE YOU NEXT YEAR. 4571 04:06:39,904 --> 04:06:39,971 4572 04:06:47,211 --> 04:06:48,412 >> THERE'S ONE OTHER PIECE I'VE 4573 04:06:48,412 --> 04:06:51,949 BEEN TASKED WITH AND I HOPE YOU 4574 04:06:51,949 --> 04:06:59,423 FORGIVE ME FOR JUST JUMPING IN 4575 04:06:59,423 --> 04:07:00,057 HERE. 4576 04:07:00,057 --> 04:07:08,733 I'M DEREK MATT THE CO-CHAIR AND 4577 04:07:08,733 --> 04:07:13,304 I WANT TO START WITH THIS. 4578 04:07:13,304 --> 04:07:15,406 THIS LAST PIECE WAS POWERFUL FOR 4579 04:07:15,406 --> 04:07:15,573 ME. 4580 04:07:15,573 --> 04:07:19,777 I RARELY GET TO HEAR FROM 4581 04:07:19,777 --> 04:07:22,880 INDUSTRY IN SPEAKING ABOUT THE 4582 04:07:22,880 --> 04:07:24,882 COLLABORATION NOT ONLY WITH THE 4583 04:07:24,882 --> 04:07:26,350 ACADEM YOU CAN INSTITUTIONS IN 4584 04:07:26,350 --> 04:07:29,253 WHICH WE INTERACT BUT ALSO 4585 04:07:29,253 --> 04:07:31,923 EXPLORING HOW TO INTERACT WITH 4586 04:07:31,923 --> 04:07:34,892 US AS COMMUNITY MEMBERS AS WELL. 4587 04:07:34,892 --> 04:07:39,430 IT'S QUITE POWERFUL TO HEAR 4588 04:07:39,430 --> 04:07:39,630 THAT. 4589 04:07:39,630 --> 04:07:43,267 AND HOPE TO HEAR MORE AT THE 4590 04:07:43,267 --> 04:07:43,901 LEVEL WITH WHICH YOU GUYS 4591 04:07:43,901 --> 04:07:44,202 OPERATE. 4592 04:07:44,202 --> 04:07:47,872 I WANTED TO SAY THAT AS WELL. 4593 04:07:47,872 --> 04:07:51,409 THE THREE BRAINY AWARDS LET'S 4594 04:07:51,409 --> 04:07:53,344 GET US OUT OF HERE. 4595 04:07:53,344 --> 04:07:59,417 THE BRAINIES GO TO WHAT WE FELT 4596 04:07:59,417 --> 04:08:03,821 WAS THE MOST POWERFUL 4597 04:08:03,821 --> 04:08:08,893 PRESENTAT 4598 04:08:08,893 --> 04:08:10,094 PRESENTATIONS OVER ALL BUT IT 4599 04:08:10,094 --> 04:08:11,429 WAS A HARD DECISION AND THERE 4600 04:08:11,429 --> 04:08:12,663 WERE WONDERFUL PRESENTATIONS. 4601 04:08:12,663 --> 04:08:15,433 OVER ALL THEY WERE ALL GREAT OF 4602 04:08:15,433 --> 04:08:18,469 COURSE AND SO IN CERTAIN WAYS 4603 04:08:18,469 --> 04:08:20,871 THIS IS JUST OFF THE TOP OF OUR 4604 04:08:20,871 --> 04:08:24,742 HEADS AS WELL. 4605 04:08:24,742 --> 04:08:33,050 THE VERY FIRST ONE GOES TO 4606 04:08:33,050 --> 04:08:33,618 DRDR 4607 04:08:33,618 --> 04:08:34,885 DRDR 4608 04:08:34,885 --> 04:08:38,222 DRDR 4609 04:08:38,222 --> 04:08:38,789 DRDR 4610 04:08:38,789 --> 04:08:40,791 DR. KULPA. 4611 04:08:40,791 --> 04:08:43,427 I WANT TO THANK HER FOR HER 4612 04:08:43,427 --> 04:08:44,095 SLIDE PRESENTATION. 4613 04:08:44,095 --> 04:08:45,429 WE'LL GET THAT TO HER. 4614 04:08:45,429 --> 04:08:48,132 AND I'LL BUTCHER THIS NAME. 4615 04:08:48,132 --> 04:08:49,333 I'M SORRY. 4616 04:08:49,333 --> 04:08:59,877 THE SECOND ONE GOES TO CATHERINE 4617 04:09:00,611 --> 04:09:00,845 RAGONELAGA. 4618 04:09:00,845 --> 04:09:10,921 YES. 4619 04:09:20,464 --> 04:09:25,603 AND DR. LETTI. 4620 04:09:25,603 --> 04:09:28,506 IS SHE HERE? 4621 04:09:28,506 --> 04:09:33,544 >> WE'LL MAKE CERTAIN SHE GETS 4622 04:09:33,544 --> 04:09:37,848 HER SLIDE. 4623 04:09:37,848 --> 04:09:39,417 THESE ARE SO SPECIAL TO US SO 4624 04:09:39,417 --> 04:09:40,785 ENJOY YOUR BRAINIES EVERYONE AND 4625 04:09:40,785 --> 04:09:41,252 HAVE A WONDERFUL TRIP. 4626 04:09:41,252 --> 04:09:51,252 THANK YOU.