1 00:00:09,548 --> 00:00:11,016 >> THANK YOU, CHRISTOPHER. 2 00:00:11,016 --> 00:00:12,718 SO WELCOME, EVERYONE. 3 00:00:12,718 --> 00:00:18,790 THIS IS OUR 16th VIRTUAL MEETING 4 00:00:18,790 --> 00:00:20,425 OF THE ARE FREDERICK NATIONAL 5 00:00:20,425 --> 00:00:21,193 LABORATORY ADVISORY COMMITTEE 6 00:00:21,193 --> 00:00:24,997 AND I WELCOME ALL OF YOU. 7 00:00:24,997 --> 00:00:28,000 I THINK THAT NEXT JULY WE MAYBE 8 00:00:28,000 --> 00:00:28,867 WILL HAVE THE OPPORTUNITY TO 9 00:00:28,867 --> 00:00:30,836 MEET EACH OTHER FACE TO FACE. 10 00:00:30,836 --> 00:00:33,672 I KNOW THIS MEETING WENT BACK 11 00:00:33,672 --> 00:00:34,439 AND FORTH AND I THINK THE 12 00:00:34,439 --> 00:00:36,575 VIRTUAL MEETINGS REALLY CAN DO 13 00:00:36,575 --> 00:00:41,113 WORK PRETTY WELL. 14 00:00:41,113 --> 00:00:44,783 SO WE DECIDED TO CO THIS IN 15 00:00:44,783 --> 00:00:48,287 FEBRUARY SO THANK YOU FOR 16 00:00:48,287 --> 00:00:48,554 ATTENDING. 17 00:00:48,554 --> 00:00:49,988 SO, THERE'S SOME DEVELOPMENTS 18 00:00:49,988 --> 00:00:51,590 SORT OF RELATED TO FNLAC I 19 00:00:51,590 --> 00:00:53,225 WANTED TO SHARE WITH YOU. 20 00:00:53,225 --> 00:00:55,394 THERE'S NO ACTION REQUIRED FOR 21 00:00:55,394 --> 00:00:55,594 THESE. 22 00:00:55,594 --> 00:00:58,130 THESE ARE JUST SORT OF 23 00:00:58,130 --> 00:00:59,565 ANNOUNCEMENTS OF SOME 24 00:00:59,565 --> 00:01:01,466 INFORMATION I THOUGHT WOULD BE 25 00:01:01,466 --> 00:01:01,700 HELPFUL. 26 00:01:01,700 --> 00:01:04,203 WARREN KIBE WILL RETURN TO THE 27 00:01:04,203 --> 00:01:06,038 NCI AS THE FIRST NCI DEPUTY 28 00:01:06,038 --> 00:01:10,776 DIRECTOR FOR DATA SCIENCE AND 29 00:01:10,776 --> 00:01:11,043 STRATEGY. 30 00:01:11,043 --> 00:01:12,177 HE'S A GREAT GUY. 31 00:01:12,177 --> 00:01:13,712 I'VE BEEN ON MANY COMMITTEES 32 00:01:13,712 --> 00:01:15,414 WITH HIM AND NCI FIRST DEPUTY 33 00:01:15,414 --> 00:01:16,782 DIRECTOR FOR DATA SCIENCE AND 34 00:01:16,782 --> 00:01:17,583 STRATEGY. 35 00:01:17,583 --> 00:01:19,985 HE WILL ADVISE DR. RATHMELL AND 36 00:01:19,985 --> 00:01:24,022 OTHER SENIOR LEADERS ON THE 37 00:01:24,022 --> 00:01:26,124 UTILIZATION AND STEWARDSHIP AND 38 00:01:26,124 --> 00:01:27,059 SHARING OF OUR MOST IMPORTANT 39 00:01:27,059 --> 00:01:29,561 TOOLS AND THAT'S DATA. 40 00:01:29,561 --> 00:01:33,465 HE'LL PROVIDE STRATEGIC 41 00:01:33,465 --> 00:01:36,335 DIRECTION, BE RESPONSIBLE FOR 42 00:01:36,335 --> 00:01:37,569 MANAGEMENT AND OVERSIGHT IN ALL 43 00:01:37,569 --> 00:01:43,542 ASPECTS OF DATA SCIENCE FOR THE 44 00:01:43,542 --> 00:01:43,809 INSTITUTE. 45 00:01:43,809 --> 00:01:45,143 WE WELCOME HIM IN THAT ROLE. 46 00:01:45,143 --> 00:01:49,581 AND ONE OF OUR MEMBERS, 47 00:01:49,581 --> 00:01:52,484 DR. BLOSSOM IMANIA IS SERVING ON 48 00:01:52,484 --> 00:01:54,286 THE BOARD OF SCIENTIFIC 49 00:01:54,286 --> 00:01:57,189 COUNSELORS AS OUR EX-OFFICIO 50 00:01:57,189 --> 00:01:59,057 REPRESENTATIVE ON FNLAC. 51 00:01:59,057 --> 00:02:00,926 HER CURRENT STINT ON THE BOARD 52 00:02:00,926 --> 00:02:02,828 OF SCIENTIFIC COUNSELORS HAS 53 00:02:02,828 --> 00:02:08,200 BEEN EXTENDED. 54 00:02:08,200 --> 00:02:16,241 SHE'LL REMAIN AND THANK YOU, 55 00:02:16,241 --> 00:02:16,475 BLOSSOM. 56 00:02:16,475 --> 00:02:23,215 WE HAVE A NEW POTENTIAL MEMBER 57 00:02:23,215 --> 00:02:27,786 MATTHEW VANDERHEIDEN APPOINTED 58 00:02:27,786 --> 00:02:29,221 JULY 14 BY DR. RATHMELL. 59 00:02:29,221 --> 00:02:38,163 HE'S HERE TODAY FOR OUR MEETING 60 00:02:38,163 --> 00:02:39,631 LISTED AS PENDING AND BELIEVE 61 00:02:39,631 --> 00:02:42,434 HE'LL BE WELCOMED IN OPENING 62 00:02:42,434 --> 00:02:42,768 STATEMENTS. 63 00:02:42,768 --> 00:02:47,039 SOME OVER ALL ANNOUNCEMENTS. 64 00:02:47,039 --> 00:02:53,078 I WANT TO REMIND YOU MUST ABSENT 65 00:02:53,078 --> 00:02:53,879 YOURSELF DURING SPECIFIC 66 00:02:53,879 --> 00:02:55,647 DISCUSSIONS WHEN PARTICIPATION 67 00:02:55,647 --> 00:03:01,687 IN THESE DELIBERATION OF A 68 00:03:01,687 --> 00:03:02,454 PRODUCT MANNER WOULD CONSTITUTE 69 00:03:02,454 --> 00:03:03,155 A CONFLICT OR CREATE THE 70 00:03:03,155 --> 00:03:08,527 APPEARANCE OF ONE. 71 00:03:08,527 --> 00:03:10,595 WE ALL KNOW WHEN WE'RE IN 72 00:03:10,595 --> 00:03:13,699 CONFLICT SO PLEASE, IF YOU FEEL 73 00:03:13,699 --> 00:03:16,201 UNEASY OR ARE IN CONFLICT IT'S 74 00:03:16,201 --> 00:03:18,737 INCUMBENT TO ADVISE THE 75 00:03:18,737 --> 00:03:19,404 EXECUTIVE SECRETARY 76 00:03:19,404 --> 00:03:20,739 DR. CHRISTOPHER KING AND ABSENT 77 00:03:20,739 --> 00:03:26,211 FROM ANY PARTICIPATION IN THAT 78 00:03:26,211 --> 00:03:34,486 SPECIFIC DISCUSSION AND 79 00:03:34,486 --> 00:03:36,288 CATEGORIES INCLUDE ALL MEMBERS 80 00:03:36,288 --> 00:03:38,256 OF THIS COMMITTEE WE MUST DEPEND 81 00:03:38,256 --> 00:03:41,626 ON YOU TO VOLUNTARILY ABSENT 82 00:03:41,626 --> 00:03:43,829 YOURSELF IN DISCUSSION MATTERS 83 00:03:43,829 --> 00:03:45,063 THAT COULD CONCEIVABLY IMPACT 84 00:03:45,063 --> 00:03:50,068 THE STATUS OF THOSE HOLDINGS AND 85 00:03:50,068 --> 00:03:51,069 WE TRUST YOUR JUDGMENT. 86 00:03:51,069 --> 00:03:52,738 WE'RE ALL FAMILIAR WITH THESE 87 00:03:52,738 --> 00:03:53,805 SORTS OF CRITERIA ON MANY 88 00:03:53,805 --> 00:03:59,811 COMMITTEES AND BOARDS WE SERVE. 89 00:03:59,811 --> 00:04:03,548 SO, PLEASE, IF IN YOU NEED TO 90 00:04:03,548 --> 00:04:05,217 MAKE YOURSELF AWARE PLEASE DO 91 00:04:05,217 --> 00:04:05,417 SO. 92 00:04:05,417 --> 00:04:06,852 MEMBERS OF THE PUBLIC WHO WISH 93 00:04:06,852 --> 00:04:08,353 TO EXPRESS VIEWS ON ITEMS 94 00:04:08,353 --> 00:04:09,087 DISCUSSED DURING THE MEET MAY DO 95 00:04:09,087 --> 00:04:15,293 SO IN WRITING TO DR. KING THE 96 00:04:15,293 --> 00:04:17,062 EXECUTIVE SECRETARY WITHIN 10 97 00:04:17,062 --> 00:04:21,500 DAYS OF THE MEETING ANY WRITTEN 98 00:04:21,500 --> 00:04:22,134 STATEMENTS WILL RECEIVE 99 00:04:22,134 --> 00:04:22,467 CONSIDERATION. 100 00:04:22,467 --> 00:04:24,336 A QUORUM IS REQUIRED FOR EACH 101 00:04:24,336 --> 00:04:29,107 INSTANCE IN WHICH A VOTE OCCURS 102 00:04:29,107 --> 00:04:30,876 DURING TODAY'S MEETING A MINIMUM 103 00:04:30,876 --> 00:04:33,345 OF EIGHT APPOINTED MEMBERS MUST 104 00:04:33,345 --> 00:04:35,247 BE PRESENT TO VOICE THEIR VOTES. 105 00:04:35,247 --> 00:04:37,616 YOU CANNOT PREDICT THE TIME OR 106 00:04:37,616 --> 00:04:39,117 OCCURRENCE FOR ANY MOTION BUT 107 00:04:39,117 --> 00:04:41,420 YOUR PRESENCE IS A MUST FOR ALL 108 00:04:41,420 --> 00:04:45,190 SEGMENTS OF THIS MEETING SO 109 00:04:45,190 --> 00:04:45,857 PLEASE, STAY TUNED. 110 00:04:45,857 --> 00:04:47,893 DON'T LEAVE YOUR POST, IF YOU 111 00:04:47,893 --> 00:04:48,093 WILL. 112 00:04:48,093 --> 00:04:50,061 AND I ASSUME, CHRIS, WE CONTINUE 113 00:04:50,061 --> 00:04:51,496 TO HAVE A QUORUM? 114 00:04:51,496 --> 00:04:52,731 >> WE DO. 115 00:04:52,731 --> 00:04:53,832 >> THANK YOU. 116 00:04:53,832 --> 00:04:55,100 SO AT THIS TIME HOPEFULLY 117 00:04:55,100 --> 00:04:57,068 EVERYONE HAS HAD A CHANCE TO 118 00:04:57,068 --> 00:05:00,872 LOOK AT THE MINUTES AROUND ARE 119 00:05:00,872 --> 00:05:03,175 THERE ANY ERRORS OR ANY ISSUES 120 00:05:03,175 --> 00:05:05,043 THAT NEED TO BE CORRECTED IN 121 00:05:05,043 --> 00:05:05,444 THOSE MINUTES? 122 00:05:05,444 --> 00:05:09,147 IF NOT, MAY I MAKE A MOTION TO 123 00:05:09,147 --> 00:05:10,782 APPROVE THE MINUTES OF THE MARCH 124 00:05:10,782 --> 00:05:16,254 11, 2024 MEETING? 125 00:05:16,254 --> 00:05:22,661 >> APPROVAL. 126 00:05:22,661 --> 00:05:24,062 >> AND A SECOND? 127 00:05:24,062 --> 00:05:25,497 >> SECOND. 128 00:05:25,497 --> 00:05:32,137 >> THANK YOU, BLOSSOM. 129 00:05:32,137 --> 00:05:33,438 ANY DISCUSSION, ANY 130 00:05:33,438 --> 00:05:33,772 DISAGREEMENT? 131 00:05:33,772 --> 00:05:34,906 ALL IN FAVOR PLEASE RAISE YOUR 132 00:05:34,906 --> 00:05:38,143 HAND OR SAY AYE. 133 00:05:38,143 --> 00:05:39,244 >> AYE. 134 00:05:39,244 --> 00:05:42,414 >> ANY ABSTENTIONS? 135 00:05:42,414 --> 00:05:43,381 ANY DISAGREEMENT? 136 00:05:43,381 --> 00:05:44,249 ANY VOTES NO? 137 00:05:44,249 --> 00:05:44,449 OKAY. 138 00:05:44,449 --> 00:05:47,252 SO WE APPROVE THE MINUTES. 139 00:05:47,252 --> 00:05:49,020 JUST TO HIGHLIGHT OUR FUTURE 140 00:05:49,020 --> 00:05:49,521 MEETING DATES. 141 00:05:49,521 --> 00:05:53,692 I JUST WANT TO CALL YOUR 142 00:05:53,692 --> 00:05:56,261 ATTENTION THAT THE NEXT FNLAC 143 00:05:56,261 --> 00:06:00,932 WILL BE HELD OCTOBER 21st 144 00:06:00,932 --> 00:06:04,302 THROUGH 22nd IN 2024 AND 145 00:06:04,302 --> 00:06:05,303 CURRENTLY PLANNED AS AN 146 00:06:05,303 --> 00:06:07,005 IN-PERSON MEETING. 147 00:06:07,005 --> 00:06:07,939 WE'LL SEE. 148 00:06:07,939 --> 00:06:09,674 HOPEFULLY WE'LL GET A CHANCE TO 149 00:06:09,674 --> 00:06:11,710 NOT ONLY MEET EACH OTHER BUT 150 00:06:11,710 --> 00:06:17,148 TOUR SOME FACILITIES FOR MANY OF 151 00:06:17,148 --> 00:06:27,692 US WOULD BE YOU'VE NEVER BEEN TO 152 00:06:29,661 --> 00:06:30,562 FREDERICK WITH THE MEETING AND 153 00:06:30,562 --> 00:06:36,101 IN OCTOBER AND THE VIRTUAL 154 00:06:36,101 --> 00:06:43,775 MEETING THERE ARE THREE MEETING 155 00:06:43,775 --> 00:06:46,945 DATES, FEBRUARY 26, JULY 13, 14 156 00:06:46,945 --> 00:06:48,847 AND OCTOBER 21, 22 WITH FEBRUARY 157 00:06:48,847 --> 00:06:49,381 BEING VIRTUAL. 158 00:06:49,381 --> 00:06:53,251 I NEED A MOTION TO APPROVE THESE 159 00:06:53,251 --> 00:06:58,757 DATES FOR 2026. 160 00:06:58,757 --> 00:06:59,724 >> SO MOVED. 161 00:06:59,724 --> 00:07:01,259 >> THANK YOU, CAROL. 162 00:07:01,259 --> 00:07:02,761 >> SECOND? 163 00:07:02,761 --> 00:07:05,630 >> SECOND. 164 00:07:05,630 --> 00:07:06,231 >> OKAY. 165 00:07:06,231 --> 00:07:08,633 I DON'T KNOW WHO DID THAT BUT 166 00:07:08,633 --> 00:07:08,900 THANK YOU. 167 00:07:08,900 --> 00:07:10,001 >> RODNEY. 168 00:07:10,001 --> 00:07:11,503 >> THANK YOU, RODNEY. 169 00:07:11,503 --> 00:07:13,171 I COULDN'T SEE YOU. 170 00:07:13,171 --> 00:07:15,941 ANY DISCUSSION? 171 00:07:15,941 --> 00:07:17,342 ALL IN FAVOR? 172 00:07:17,342 --> 00:07:18,443 OPPOSED? 173 00:07:18,443 --> 00:07:18,610 THE. 174 00:07:18,610 --> 00:07:24,249 WE APPROVE THE MEETING FOR NEXT 175 00:07:24,249 --> 00:07:28,253 YEAR SO IT'S MY PLEASURE TO 176 00:07:28,253 --> 00:07:33,558 INTRODUCE DR. KIM RATHMELL WHO 177 00:07:33,558 --> 00:07:37,028 IS GOING TO GIVE THE NCI 178 00:07:37,028 --> 00:07:37,662 DIRECTOR'S REPORT. 179 00:07:37,662 --> 00:07:38,863 >> THANK YOU VERY MUCH. 180 00:07:38,863 --> 00:07:40,765 WELCOME AND I AM LOOKING FORWARD 181 00:07:40,765 --> 00:07:45,704 TO WHEN WE HAVE OUR NEXT, FIRST 182 00:07:45,704 --> 00:07:46,671 FOR ME, IN-PERSON MEETING. 183 00:07:46,671 --> 00:07:47,739 I APPRECIATE ALL THE WORK YOU 184 00:07:47,739 --> 00:07:48,506 DO. 185 00:07:48,506 --> 00:07:50,642 YOU CAN MOVE TO THE NEXT SLIDE. 186 00:07:50,642 --> 00:07:52,410 THAT WILL JUST GIVE SOME OF OUR 187 00:07:52,410 --> 00:07:53,345 OVERVIEW OF WHAT WE'RE GOING TO 188 00:07:53,345 --> 00:07:54,879 TALK ABOUT TODAY. 189 00:07:54,879 --> 00:08:00,185 I'VE BEEN IN THE ROLE NOW ABOUT 190 00:08:00,185 --> 00:08:04,856 SIX MONTHS AND I'VE BEEN 191 00:08:04,856 --> 00:08:06,458 LISTENING AND LEARNING A LOT AND 192 00:08:06,458 --> 00:08:08,159 GATHERING DATA AND WHAT WE CAN 193 00:08:08,159 --> 00:08:09,461 AND CAN'T DO AND WE'LL TALK 194 00:08:09,461 --> 00:08:11,262 ABOUT RECENT NEWS AND UPDATES. 195 00:08:11,262 --> 00:08:19,871 ALWAYS A HOT TOPIC IS BUDGET AND 196 00:08:19,871 --> 00:08:22,741 WE'LL ALSO TALK ABOUT 197 00:08:22,741 --> 00:08:23,575 DEVELOPMENTS WITH THE FREDERICK 198 00:08:23,575 --> 00:08:24,175 NATIONAL LAB. 199 00:08:24,175 --> 00:08:26,745 IT'S BEEN A TOUGH BUDGET YEAR 200 00:08:26,745 --> 00:08:31,883 AND I'LL EMPHASIZE WE'RE NOT 201 00:08:31,883 --> 00:08:33,485 SLOWING DOWN AND LEARNING TO BE 202 00:08:33,485 --> 00:08:34,753 MORE CREATIVE BUT WE'RE EXCITED 203 00:08:34,753 --> 00:08:36,655 ABOUT ALL THE THINGS THAT ARE 204 00:08:36,655 --> 00:08:39,024 HAPPENING. 205 00:08:39,024 --> 00:08:39,891 AND THE OTHER IS THAT Q&A WILL 206 00:08:39,891 --> 00:08:41,192 BE AT THE END. 207 00:08:41,192 --> 00:08:42,761 WE DO WENT TO HEAR FROM YOU AND 208 00:08:42,761 --> 00:08:46,765 GET YOUR THOUGHTS ON HOW WE DO 209 00:08:46,765 --> 00:08:54,506 THIS BEST. 210 00:08:54,506 --> 00:08:58,743 FIRST OFF YOU ALREADY HEARD 211 00:08:58,743 --> 00:09:07,619 DR. VANDER HEIDEN IS FROM M.I.T. 212 00:09:07,619 --> 00:09:11,456 AND WILL SOON BE A PERMANENT 213 00:09:11,456 --> 00:09:14,159 MEMBER AND LOOKING FORWARD TO 214 00:09:14,159 --> 00:09:16,094 YOUR EXPERT COUNSEL WHILE 215 00:09:16,094 --> 00:09:20,098 SERVING ON THE FNLAC SO WELCOME. 216 00:09:20,098 --> 00:09:22,934 MOVING ON TO THE RECENT NEWS AND 217 00:09:22,934 --> 00:09:26,004 UPDATES. 218 00:09:26,004 --> 00:09:28,773 THE FIRST IS RELEVANT FOR MATT 219 00:09:28,773 --> 00:09:29,107 SPECIFICALLY. 220 00:09:29,107 --> 00:09:30,341 THOUGH YOU ALL HAVE AN 221 00:09:30,341 --> 00:09:31,876 ORIENTATION TO THE BOARD THAT 222 00:09:31,876 --> 00:09:34,713 YOU SERVE ON, ONE OF THE THINGS 223 00:09:34,713 --> 00:09:37,482 THAT WE'VE REALIZED IS THIS IS A 224 00:09:37,482 --> 00:09:39,451 BIG ORGANIZATION AND. 225 00:09:39,451 --> 00:09:41,920 THERE'S A LOT OF PIECES AND THAT 226 00:09:41,920 --> 00:09:43,855 BOARD MEMBERS MAY BE MOST 227 00:09:43,855 --> 00:09:49,027 EFFECTIVE IF WE GIVE THEM A BIG 228 00:09:49,027 --> 00:09:50,195 INTRODUCTION TO WHAT HAPPENS 229 00:09:50,195 --> 00:09:50,462 HERE. 230 00:09:50,462 --> 00:09:54,232 SO WE'RE PLANNING A MIXED 231 00:09:54,232 --> 00:09:57,635 ORIENTATION FOR ALL NCI BOARD 232 00:09:57,635 --> 00:09:59,070 MEMBERS AND I HAVE SIX BOARDS. 233 00:09:59,070 --> 00:10:04,642 AS PEOPLE COME ON WE'LL BE 234 00:10:04,642 --> 00:10:05,677 CREATING THIS OPPORTUNITY TO LET 235 00:10:05,677 --> 00:10:09,581 PEOPLE IN ON REALLY HOW THIS 236 00:10:09,581 --> 00:10:11,316 MESSAGE GETS ACROSS THE WHOLE 237 00:10:11,316 --> 00:10:12,817 SPACE SO THE BOARDS CAN WORK 238 00:10:12,817 --> 00:10:13,752 MOST EFFECTIVELY. 239 00:10:13,752 --> 00:10:14,986 SO NEW MEMBERS WILL TAKE 240 00:10:14,986 --> 00:10:20,458 ADVANTAGE OF THAT. 241 00:10:20,458 --> 00:10:24,329 ALL RIGHT, SO PROBABLY THE THING 242 00:10:24,329 --> 00:10:25,530 YOU'RE MOST CURIOUS ABOUT I 243 00:10:25,530 --> 00:10:26,865 CAN'T TELL YOU MUCH ABOUT 244 00:10:26,865 --> 00:10:33,037 BECAUSE IT'S IN THE MIDDLE OF IT 245 00:10:33,037 --> 00:10:37,142 IS THIS IS WHAT GOES UNDER 246 00:10:37,142 --> 00:10:39,344 COMPETITION PERIODICALLY STILL 247 00:10:39,344 --> 00:10:40,779 IN THE NEGOTIATION PHASE. 248 00:10:40,779 --> 00:10:42,313 IT'S AT THE PACE THAT'S BEEN 249 00:10:42,313 --> 00:10:43,581 EXPECTED FOR SOME TIME. 250 00:10:43,581 --> 00:10:48,987 AND THAT'S WHAT I CAN TELL YOU. 251 00:10:48,987 --> 00:10:50,555 IN TERMS OF DATES THAT I CAN LET 252 00:10:50,555 --> 00:10:52,690 YOU KNOW THE ORIGINAL PROPOSALS 253 00:10:52,690 --> 00:10:55,360 WERE DUE IN FEBRUARY 2023. 254 00:10:55,360 --> 00:10:57,562 THERE WAS A PERIOD OF TECHNICAL 255 00:10:57,562 --> 00:10:59,364 PEER REVIEW THAT OCCURRED 256 00:10:59,364 --> 00:11:05,370 SHORTLY AFTER THAT. 257 00:11:05,370 --> 00:11:10,775 NEGOTIATIONS OPENED UP IN JUNE 258 00:11:10,775 --> 00:11:20,685 AND ALL RIGHT. 259 00:11:20,685 --> 00:11:23,688 THE TOPIC THAT COMES UP 260 00:11:23,688 --> 00:11:25,190 FREQUENTLY WE USE LOTS OF 261 00:11:25,190 --> 00:11:26,491 COMPONENTS OF FREDERICK IN LOTS 262 00:11:26,491 --> 00:11:27,525 OF THE WORK WE DO. 263 00:11:27,525 --> 00:11:29,561 I WANTED TO LET YOU KNOW ABOUT 264 00:11:29,561 --> 00:11:38,403 THE DEPUTY SECRETARY FOR HHS AND 265 00:11:38,403 --> 00:11:42,140 I HAD A MEETING WITH HER AND SHE 266 00:11:42,140 --> 00:11:44,809 HAD SEVERAL QUESTIONS AND WERE 267 00:11:44,809 --> 00:11:46,744 TALKING ABOUT WHAT ACTIVITIES 268 00:11:46,744 --> 00:11:48,513 HAPPEN AT THE FREDERICK NATIONAL 269 00:11:48,513 --> 00:11:52,984 LABS AND WE FOCUSSED THE 270 00:11:52,984 --> 00:11:53,985 ENTIRETY OF THE MEETING WITH HER 271 00:11:53,985 --> 00:11:58,156 ON WHAT WE DO IN TERMS OF THE 272 00:11:58,156 --> 00:12:05,363 BENCH TO BEDSIDE AND BACK 273 00:12:05,363 --> 00:12:07,465 APPROACH TO CONQUERING CANCER 274 00:12:07,465 --> 00:12:09,300 AND HAD AN OVERVIEW AT THE 275 00:12:09,300 --> 00:12:13,004 FREDERICK NATIONAL LIBRARY WITH 276 00:12:13,004 --> 00:12:17,408 HER AND SHE ASKED POIGNANT 277 00:12:17,408 --> 00:12:22,113 QUESTIONS AND WAS ENGAGED AND 278 00:12:22,113 --> 00:12:24,315 INTERESTING AND TOOK HER TO THE 279 00:12:24,315 --> 00:12:28,253 MARSHAL LINNAHAN LABORATORY TO 280 00:12:28,253 --> 00:12:30,655 SHOW HER SCIENCE IN ACTION. 281 00:12:30,655 --> 00:12:32,690 IT WAS A PRODUCTIVE VISIT AND I 282 00:12:32,690 --> 00:12:35,059 THINK WHAT WE HAVE TO DO TO HELP 283 00:12:35,059 --> 00:12:35,760 FOLKS IN GOVERNMENT AND KNOW 284 00:12:35,760 --> 00:12:37,428 WHAT WE NEED IN TERMS OF POLICY 285 00:12:37,428 --> 00:12:40,798 AND FUNDING, IN TERMS OF AGENDA 286 00:12:40,798 --> 00:12:41,432 SETTING ABOUT THE WORK THAT WE 287 00:12:41,432 --> 00:12:46,404 DO. 288 00:12:46,404 --> 00:12:47,605 THAT WAS A BIG INITIATIVE IN 289 00:12:47,605 --> 00:12:52,343 HOSTING HER FOR HALF A DAY. 290 00:12:52,343 --> 00:12:54,646 SO WE ALSO CARRY THAT TORCH IN 291 00:12:54,646 --> 00:13:00,184 OTHER PLACES LIKE AUCR AND ASCO 292 00:13:00,184 --> 00:13:02,320 IN TERMS OF MEETINGS WE HAVE A 293 00:13:02,320 --> 00:13:04,055 LARGE FOOTPRINT IN. 294 00:13:04,055 --> 00:13:05,490 IT'S INSPIRING FOR ME TO GO TO 295 00:13:05,490 --> 00:13:06,791 THESE MEETINGS IN THIS NEW 296 00:13:06,791 --> 00:13:09,160 CAPACITY AND SEE THE ENERGY AND 297 00:13:09,160 --> 00:13:12,230 PASSION THAT THERE IS ARRANGE 298 00:13:12,230 --> 00:13:13,197 CANCER RESEARCH IN SO MANY 299 00:13:13,197 --> 00:13:16,434 DIFFERENT ARENAS. 300 00:13:16,434 --> 00:13:18,469 WE HAD TWO OF OUR NCI STAFF 301 00:13:18,469 --> 00:13:20,672 RECOGNIZED FOR SIGNIFICANT 302 00:13:20,672 --> 00:13:22,640 CONTRIBUTIONS AT ACR. 303 00:13:22,640 --> 00:13:24,008 STEVE ROSENBERG RECEIVE THE LIFE 304 00:13:24,008 --> 00:13:27,612 TIME ACHIEVEMENT AWARD FOR 305 00:13:27,612 --> 00:13:33,051 CANCER RESEARCH AND ASCO WON THE 306 00:13:33,051 --> 00:13:38,089 HUMANITARIAN AWARD. 307 00:13:38,089 --> 00:13:41,793 IN ADDITION TO LOTS OF POSTERS 308 00:13:41,793 --> 00:13:47,198 AND PRESENTATIONS AND OTHER 309 00:13:47,198 --> 00:13:57,041 NETWORK 310 00:13:57,041 --> 00:14:00,445 NETWORKING NCI STRIVES TO BE 311 00:14:00,445 --> 00:14:02,947 FRONT AND CENTER AND WE THINK 312 00:14:02,947 --> 00:14:04,182 BROADLY AND A DIFFERENT APPROACH 313 00:14:04,182 --> 00:14:04,916 TO RESEARCH. 314 00:14:04,916 --> 00:14:07,018 WE CALL OUT A NEW ERA. 315 00:14:07,018 --> 00:14:08,753 THIS WAS STILL EARLY IN MY 316 00:14:08,753 --> 00:14:12,190 TENURE AND I USED AN ANALOGY OF 317 00:14:12,190 --> 00:14:14,325 THE TAILOR SWIFT ERAS TO SUGGEST 318 00:14:14,325 --> 00:14:24,802 WE'RE MOVING INTO AN ERA OF. 319 00:14:25,136 --> 00:14:26,437 RESEARCH AND MORE TRANSPARENCY 320 00:14:26,437 --> 00:14:31,609 PARTICULARLY AMONG GROUPS THAT 321 00:14:31,609 --> 00:14:42,153 HAVE NOT HISTORICALLY WE ENGAGE 322 00:14:53,464 --> 00:14:54,832 DIFFERENT STAKEHOLDERS AND 323 00:14:54,832 --> 00:15:01,506 ADVOCATES AND THINK OF 324 00:15:01,506 --> 00:15:02,607 DISTRIBUTED CLINICAL TRIAL 325 00:15:02,607 --> 00:15:13,051 DESIGN BEING FORWARD FROM 326 00:15:14,118 --> 00:15:17,622 DISCOVERY TO CARE MOVING MORE 327 00:15:17,622 --> 00:15:21,059 QUICKLY BECAUSE WE HAVE GOOD 328 00:15:21,059 --> 00:15:23,027 OPPORTUNITIES TO ADVANCE PATIENT 329 00:15:23,027 --> 00:15:23,661 CARE. 330 00:15:23,661 --> 00:15:27,131 THERE WAS A LOT OF ENTHUSIASM 331 00:15:27,131 --> 00:15:30,668 FOR WE CAN DO IT THESE THINGS 332 00:15:30,668 --> 00:15:31,302 FASTER. 333 00:15:31,302 --> 00:15:34,739 JUST TO LET YOU KNOW ABOUT A 334 00:15:34,739 --> 00:15:36,741 COUPLE TRANSITIONS IN OUR 335 00:15:36,741 --> 00:15:38,743 INTRAMURAL PROGRAM. 336 00:15:38,743 --> 00:15:40,344 ONE BIG PART OF THE INTRAMURAL 337 00:15:40,344 --> 00:15:47,852 PROGRAM IS CCR THE CANCER 338 00:15:47,852 --> 00:15:55,793 RESEARCH AND TOMB MISTELI HAS 339 00:15:55,793 --> 00:15:58,763 LED THIS AND BECAUSE IT'S A 340 00:15:58,763 --> 00:16:00,998 LARGE FOOTPRINT OF BASIC AND 341 00:16:00,998 --> 00:16:02,400 CLINICAL RESEARCH WE'RE 342 00:16:02,400 --> 00:16:04,802 OPERATING WITH A CO-DIRECTOR 343 00:16:04,802 --> 00:16:05,002 MODEL. 344 00:16:05,002 --> 00:16:09,440 JAMES GULLEY WAS CO-DIRECTING 345 00:16:09,440 --> 00:16:13,044 WITH GLENN UNTIL HIS RETIREMENT 346 00:16:13,044 --> 00:16:19,884 AND NOW IT'S DR. CAROL THIE LE 347 00:16:19,884 --> 00:16:21,919 AND WHILE LOOK TO FILL THAT 348 00:16:21,919 --> 00:16:23,754 POSITION IN THE NEXT YEAR. 349 00:16:23,754 --> 00:16:24,989 YOU ALREADY HEARD ABOUT 350 00:16:24,989 --> 00:16:25,323 DR. KIBBI. 351 00:16:25,323 --> 00:16:30,695 WE'RE EXCITED FOR THE INAUGURAL 352 00:16:30,695 --> 00:16:32,430 DEPUTY DIRECTOR FOR DATA SCIENCE 353 00:16:32,430 --> 00:16:33,498 AND STRATEGY. 354 00:16:33,498 --> 00:16:36,033 AS YOU HEARD IT WILL BE ABOUT 355 00:16:36,033 --> 00:16:38,269 ALL THINGS DATA. 356 00:16:38,269 --> 00:16:41,706 SO ADVISING ON A.I., DATA 357 00:16:41,706 --> 00:16:44,609 HARMONIZATION AND COMMON DATA 358 00:16:44,609 --> 00:16:45,877 ELEMENTS WILL HAVE A BIG ROLE IN 359 00:16:45,877 --> 00:16:51,849 THINGS WE DO AT FREDERICK 360 00:16:51,849 --> 00:16:52,617 NATIONAL LAB. 361 00:16:52,617 --> 00:16:56,487 AND WE ALSO BROUGHT ON A SENIOR 362 00:16:56,487 --> 00:16:58,523 ADVISER FOR CLINICAL RESEARCH 363 00:16:58,523 --> 00:17:02,560 AND THIS GETS TO THE INITIATIVE 364 00:17:02,560 --> 00:17:04,996 TO TRY TO DEVELOP A CLINICAL 365 00:17:04,996 --> 00:17:08,065 TRIAL FLASHING CAN BE MORE 366 00:17:08,065 --> 00:17:10,768 SIMPLE WITH DR. SHAALAN BEG AND 367 00:17:10,768 --> 00:17:14,739 HE IS WORKING ACROSS THE 368 00:17:14,739 --> 00:17:19,310 CLINICAL RESEARCH SPACE TO HELP 369 00:17:19,310 --> 00:17:21,412 US TO MODERNIZE IN ALL THESE 370 00:17:21,412 --> 00:17:22,613 AREAS. 371 00:17:22,613 --> 00:17:25,049 HE STARTED IN THE LAST FEW WEEKS 372 00:17:25,049 --> 00:17:27,351 GETTING TO KNOW PEOPLE THAT WERE 373 00:17:27,351 --> 00:17:28,286 LOOKING AT ALL AREAS OF CLINICAL 374 00:17:28,286 --> 00:17:34,692 RESEARCH ACTIVITY. 375 00:17:34,692 --> 00:17:37,562 THEN ALSO IT'S NOT ALWAYS JUST 376 00:17:37,562 --> 00:17:41,832 ABOUT NEW INDIVIDUAL LEADERS BUT 377 00:17:41,832 --> 00:17:44,001 DIFFERENT WAYS THAT WE ORGANIZE 378 00:17:44,001 --> 00:17:47,004 THE ORGANIZATION AND BUILDING 379 00:17:47,004 --> 00:17:52,043 LEADERSHIP AND LEADERSHIP 380 00:17:52,043 --> 00:17:56,347 COMMUNICATION. 381 00:17:56,347 --> 00:18:00,985 WE CHANGED THE NAME TO THE 382 00:18:00,985 --> 00:18:04,188 CENTER TO CHANGE CANCER 383 00:18:04,188 --> 00:18:05,289 DISPARITIES TO CANCER HEALTH 384 00:18:05,289 --> 00:18:05,523 EQUITY. 385 00:18:05,523 --> 00:18:07,291 THERE WAS A BIG INITIATIVE TO 386 00:18:07,291 --> 00:18:08,659 BRING TOGETHER A GROUP OF CANCER 387 00:18:08,659 --> 00:18:12,730 EQUITY LEADERS, C.E.L. IS THE 388 00:18:12,730 --> 00:18:14,165 GROUP ON THE LEFT. 389 00:18:14,165 --> 00:18:18,803 THESE ARE ALL LEADERS WHO 390 00:18:18,803 --> 00:18:20,104 DEDICATED THEIR CAREERS TO 391 00:18:20,104 --> 00:18:22,773 ADVANCING EQUITY ACROSS THE 392 00:18:22,773 --> 00:18:27,345 BOARD FROM WORKFORCE TO PATIENT 393 00:18:27,345 --> 00:18:33,718 CARE SO THIS GROUP IS HELPING 394 00:18:33,718 --> 00:18:42,693 ADVISE US HOW WE BRING EQUITY 395 00:18:42,693 --> 00:18:44,562 MORE BROADLY AND THE FIRST IT 396 00:18:44,562 --> 00:18:47,465 BLACK IN CANCER CONFERENCE HELD 397 00:18:47,465 --> 00:18:50,534 BY THE FREDERICK NATIONAL LABS 398 00:18:50,534 --> 00:18:51,002 AND BROUGHT TOGETHER 399 00:18:51,002 --> 00:18:54,472 INVESTIGATORS FROM AROUND THE 400 00:18:54,472 --> 00:18:58,743 COUNTRY TO TALK ABOUT ISSUES 401 00:18:58,743 --> 00:19:01,912 THAT FACE YOUNG PEOPLE GOING 402 00:19:01,912 --> 00:19:07,318 INTO CANCER FIELDS, CANCER 403 00:19:07,318 --> 00:19:08,286 PATIENTS FROM DIFFERENT 404 00:19:08,286 --> 00:19:10,087 COMMUNITIES AND IT WAS REALLY 405 00:19:10,087 --> 00:19:11,255 WELL DONE. 406 00:19:11,255 --> 00:19:16,761 VERY WELL ATTENDED AND DEFINITE 407 00:19:16,761 --> 00:19:25,069 LY A SPECIAL EVENT. 408 00:19:25,069 --> 00:19:26,771 GLAD FREDERICK NATIONAL LAB ED 409 00:19:26,771 --> 00:19:27,171 THIS. 410 00:19:27,171 --> 00:19:29,240 I MENTION THE NAME CHANGE 411 00:19:29,240 --> 00:19:29,473 COMING. 412 00:19:29,473 --> 00:19:31,609 WE'VE BEEN TALKING ABOUT IT SO 413 00:19:31,609 --> 00:19:32,476 MUCH IT'S ALREADY THE PREFERRED 414 00:19:32,476 --> 00:19:34,578 NAME IS THE CENTER FOR CANCER 415 00:19:34,578 --> 00:19:37,348 HEALTH EQUITY, CCHE. 416 00:19:37,348 --> 00:19:40,951 SO THIS IS A GROUP THAT TAKES ON 417 00:19:40,951 --> 00:19:43,220 ALL OF OUR HEALTH EQUITY 418 00:19:43,220 --> 00:19:46,757 INITIATIVES AND LED BY 419 00:19:46,757 --> 00:19:49,460 DR. SPRINGFIELD. 420 00:19:49,460 --> 00:19:54,532 OKAY, LET'S TALK ABOUT BUDGETS. 421 00:19:54,532 --> 00:19:55,933 JUST TO LEVEL SET WHERE THINGS 422 00:19:55,933 --> 00:19:59,970 ARE WITH BUDGET, THE TWO COLUMNS 423 00:19:59,970 --> 00:20:00,838 THE FIRST COLUMN ACTUALLY THE 424 00:20:00,838 --> 00:20:03,607 ONE THERE IN THE MIDDLE IS OUR 425 00:20:03,607 --> 00:20:06,744 OPPORTUNITY EVERY YEAR TO PUT 426 00:20:06,744 --> 00:20:07,878 OUT WHAT WE THINK IT WOULD COST 427 00:20:07,878 --> 00:20:09,647 TO DO THE WORK THAT WE'RE DOING. 428 00:20:09,647 --> 00:20:13,851 SCIENCE GETS MORE EXPENSIVE, 429 00:20:13,851 --> 00:20:14,752 THINGS COST MORE. 430 00:20:14,752 --> 00:20:17,455 THE KINDS OF THINGS THAT WE DO 431 00:20:17,455 --> 00:20:20,024 PARTICULARLY IN RESEARCH BASED 432 00:20:20,024 --> 00:20:23,861 AND IN BASIC SCIENCE JUST ADDS 433 00:20:23,861 --> 00:20:25,296 UP. 434 00:20:25,296 --> 00:20:28,265 YOU CAN SEE IN IN FY23 OUR 435 00:20:28,265 --> 00:20:30,468 ESTIM 436 00:20:30,468 --> 00:20:34,672 ESTIMATE WAS 7.7 AND THEEST PLAT 437 00:20:34,672 --> 00:20:38,709 FOR WILL FY2025 IS 11.46. 438 00:20:38,709 --> 00:20:40,945 THE DELTA IS GETTING BIG. 439 00:20:40,945 --> 00:20:43,781 IN FY23 WE RECEIVED $7.3 BILLION 440 00:20:43,781 --> 00:20:46,751 INCLUDING THE LAST YEAR OF CURES 441 00:20:46,751 --> 00:20:48,119 ACT FUNDING. 442 00:20:48,119 --> 00:20:50,554 AND IN FY24 THE BUDGET WE'RE 443 00:20:50,554 --> 00:20:53,924 OPERATING IN TODAY, WE RECEIVED 444 00:20:53,924 --> 00:20:56,994 AN APPROPRIATION OF $7.22 445 00:20:56,994 --> 00:20:57,228 BILLION. 446 00:20:57,228 --> 00:20:59,463 THAT REFLECTED AN INCREASE IN 447 00:20:59,463 --> 00:21:06,771 OUR BASE OF $120 MILLION, WHICH 448 00:21:06,771 --> 00:21:13,811 DOES WHICH REPRESENTS AN 449 00:21:13,811 --> 00:21:14,545 ACKNOWLEDGEMENT THINGS COST MORE 450 00:21:14,545 --> 00:21:16,614 AND ATTENTION TO THE FACT THEY 451 00:21:16,614 --> 00:21:20,284 DIDN'T WANT THE EXTRAMURAL 452 00:21:20,284 --> 00:21:24,221 FUNDING TO BE HARMED BY THE 453 00:21:24,221 --> 00:21:25,523 CHALLENGING GRANT SITUATION. 454 00:21:25,523 --> 00:21:29,026 NEVERTHELESS, IT WAS A $96 455 00:21:29,026 --> 00:21:31,829 MILLION DECREASE IN EFFECTIVE 456 00:21:31,829 --> 00:21:32,062 DOLLARS. 457 00:21:32,062 --> 00:21:33,931 A DIFFERENT KIND FROM THE YEAR 458 00:21:33,931 --> 00:21:34,298 BEFORE. 459 00:21:34,298 --> 00:21:39,603 THIS IS THE FIRST DECREASE WE'VE 460 00:21:39,603 --> 00:21:42,473 HAD IN QUITE SOME TIME SO IT'S 461 00:21:42,473 --> 00:21:43,541 MADE IT A PARTICULARLY 462 00:21:43,541 --> 00:21:45,242 CHALLENGING YEAR WHEN WE KNOW 463 00:21:45,242 --> 00:21:46,911 THE COST OF DOING THIS WORK IS 464 00:21:46,911 --> 00:21:48,112 QUITE A LOT MORE. 465 00:21:48,112 --> 00:21:52,149 WE'LL FIND OUT FOR FY25 SOME 466 00:21:52,149 --> 00:21:55,920 TIME AFTER OCTOBER 1. 467 00:21:55,920 --> 00:21:58,756 BUT I WILL SAY THE PRESIDENT'S 468 00:21:58,756 --> 00:22:00,558 BUDGET PROPOSAL WAS FOR ALMOST 469 00:22:00,558 --> 00:22:03,327 $9.3 BILLION. 470 00:22:03,327 --> 00:22:04,562 WE WILL WAIT AND SEE. 471 00:22:04,562 --> 00:22:07,531 THIS IS LIKELY TO BE A TOUGH 472 00:22:07,531 --> 00:22:07,731 YEAR. 473 00:22:07,731 --> 00:22:10,768 THE DEBT CEILING IS STILL IN 474 00:22:10,768 --> 00:22:15,706 PLACE AND THAT'S STILL A 475 00:22:15,706 --> 00:22:17,341 REQUIREMENT FOR PLANNING THE 476 00:22:17,341 --> 00:22:23,547 BUDGET OVER ALL FOR ALL OF THE 477 00:22:23,547 --> 00:22:24,648 GOVERNMENT. 478 00:22:24,648 --> 00:22:27,418 WHAT THAT HAS TRANSLATED FOR US, 479 00:22:27,418 --> 00:22:28,552 IT'S EASIEST TO LOOK WHERE THE 480 00:22:28,552 --> 00:22:33,257 EFFECTS ARE IN OUR PAY LINES. 481 00:22:33,257 --> 00:22:35,793 THIS IS FOR EXTRAMURAL PROGRAMS. 482 00:22:35,793 --> 00:22:38,696 WE TEND TO HAVE KEPT THINGS LIKE 483 00:22:38,696 --> 00:22:44,635 THE FREDERICK NATIONAL LAB 484 00:22:44,635 --> 00:22:45,536 ROUGHLY FLAT. 485 00:22:45,536 --> 00:22:47,972 THE PAY LINES IS WHERE WE MAKE 486 00:22:47,972 --> 00:22:49,740 SEM YEAR TO YEAR. 487 00:22:49,740 --> 00:22:52,510 THE AVERAGE FOR ESTABLISHED 488 00:22:52,510 --> 00:22:54,745 INVESTIGATORS WHICH YOU SEE IN 489 00:22:54,745 --> 00:22:58,015 THE DARKER COLORED LINE HAS BEEN 490 00:22:58,015 --> 00:23:00,918 HOVERING AROUND 10, A 10% PAY 491 00:23:00,918 --> 00:23:01,118 LINE. 492 00:23:01,118 --> 00:23:03,187 OF COURSE THE FUNDING RATE IS 493 00:23:03,187 --> 00:23:03,420 HIGHER. 494 00:23:03,420 --> 00:23:06,423 IT COMES FROM SOME SELECT PAY 495 00:23:06,423 --> 00:23:07,291 AND FROM RFAs THAT COME IN AS 496 00:23:07,291 --> 00:23:17,401 WELL. 497 00:23:22,339 --> 00:23:25,376 WE FELT WE STILL NEEDED TO MAKE 498 00:23:25,376 --> 00:23:27,278 A PRIORITY AND KEPT IT AT 17% 499 00:23:27,278 --> 00:23:31,682 FOR INVESTIGATORS. 500 00:23:31,682 --> 00:23:33,517 IT'S A 7% ADVANTAGE FOR BEING AN 501 00:23:33,517 --> 00:23:43,961 EARLY STAGE INVESTIGATOR. 502 00:23:45,496 --> 00:23:47,064 SO, WHEN WE HAVE A TOUGH BUDGET 503 00:23:47,064 --> 00:23:48,899 SITUATION IT'S IMPORTANT TO 504 00:23:48,899 --> 00:23:49,199 PRIORITIZE. 505 00:23:49,199 --> 00:23:50,501 WE HAVE A NATIONAL CANCER PLAN 506 00:23:50,501 --> 00:23:51,068 IT'S A YEAR OLD. 507 00:23:51,068 --> 00:23:53,938 I FOUND IT TO BE VERY HELPFUL. 508 00:23:53,938 --> 00:23:55,272 WHEN I THINK ABOUT HOW TO 509 00:23:55,272 --> 00:23:59,810 PRIORITIZE THE WORK THAT WE DO 510 00:23:59,810 --> 00:24:01,378 AROUND THESE EIGHT GOALS 511 00:24:01,378 --> 00:24:02,379 ARTICULATED FOR THEM 512 00:24:02,379 --> 00:24:04,081 REPRESENTING HEALTH CENTERED 513 00:24:04,081 --> 00:24:06,684 GOALS AND FOR WHAT I CALL 514 00:24:06,684 --> 00:24:10,120 EMPOWERING GOALS BUT YOU CAN SEE 515 00:24:10,120 --> 00:24:11,855 HOW SORT OF A ROAD MAP LIKE THIS 516 00:24:11,855 --> 00:24:13,724 GIVES US SOME OF THE DIRECTION 517 00:24:13,724 --> 00:24:16,026 AND ENERGY FOR WHERE WE'RE GOING 518 00:24:16,026 --> 00:24:20,564 TO PUT OUR RESOURCES BECAUSE WE 519 00:24:20,564 --> 00:24:22,566 DO HAVE THESE GOALS AT THE END 520 00:24:22,566 --> 00:24:24,602 WHICH IS TO IMPROVE HEALTH 521 00:24:24,602 --> 00:24:27,705 OUTCOMES FOR EVERYONE AND TO 522 00:24:27,705 --> 00:24:29,440 REDUCE CANCER MORTALITY BY 50% 523 00:24:29,440 --> 00:24:32,009 BY 2047 SO WE NEED TO MAKE 524 00:24:32,009 --> 00:24:33,477 PROGRESS ACROSS PREVENTION, 525 00:24:33,477 --> 00:24:35,546 EARLY DETECTION, DELIVERING 526 00:24:35,546 --> 00:24:38,682 OPTIMAL CARE, DEVELOPING INFECT 527 00:24:38,682 --> 00:24:42,119 WILL THERAPIES AND ELIMINATING 528 00:24:42,119 --> 00:24:42,419 INEQUITIES. 529 00:24:42,419 --> 00:24:43,253 HUGE PORTIONS OF THE POPULATIONS 530 00:24:43,253 --> 00:24:45,889 TO MAKE BIG IMPROVEMENTS. 531 00:24:45,889 --> 00:24:47,458 MAXIMIZING DATA UTILITY AND 532 00:24:47,458 --> 00:24:50,761 OPTIMIZING THE WORKFORCE AND 533 00:24:50,761 --> 00:24:53,530 ENGAGING EVERY PERSON. 534 00:24:53,530 --> 00:24:54,498 AND WITH THAT IN THE BUDGET 535 00:24:54,498 --> 00:24:56,467 SECTION I THOUGHT I'D SHARE WHAT 536 00:24:56,467 --> 00:24:58,736 I FIND TO BE HELPFUL TO HAVE A 537 00:24:58,736 --> 00:25:02,139 SET OF VALUES THAT I LEAN ON 538 00:25:02,139 --> 00:25:03,340 WHEN I'M WORKING ON MAKING SOME 539 00:25:03,340 --> 00:25:07,678 OF THESE DECISIONS AND FOR ME 540 00:25:07,678 --> 00:25:08,712 THAT'S TALENT DEVELOPMENT SO 541 00:25:08,712 --> 00:25:10,247 THEN NO SURPRISE THAT'S WHY WE 542 00:25:10,247 --> 00:25:12,182 KEPT THE PAY LINE FOR EARLY 543 00:25:12,182 --> 00:25:17,521 STAGE INVESTIGATORS AT 17% AND 544 00:25:17,521 --> 00:25:20,924 ALSO HELD FUNDING FOR TRAINING 545 00:25:20,924 --> 00:25:22,960 PROGRAMS AND KEPT THAT FROM 546 00:25:22,960 --> 00:25:25,329 BEING CUT WHERE EVERYTHING ELSE 547 00:25:25,329 --> 00:25:26,163 SAW A CUT. 548 00:25:26,163 --> 00:25:28,298 THE OTHER VALUES FOR ME ARE 549 00:25:28,298 --> 00:25:29,733 CREATIVITY AND INNOVATION. 550 00:25:29,733 --> 00:25:31,969 THAT COMES IN VERY HANDY WHEN 551 00:25:31,969 --> 00:25:34,738 WE'RE HAVING A TOUGH BUDGET 552 00:25:34,738 --> 00:25:36,407 TIME. 553 00:25:36,407 --> 00:25:37,641 EMPOWERMENT AND ENABLING 554 00:25:37,641 --> 00:25:40,177 EVERYONE TO BE A PART OF THIS 555 00:25:40,177 --> 00:25:41,679 EFFORT AND FISCAL 556 00:25:41,679 --> 00:25:44,114 RESPONSIBILITY. 557 00:25:44,114 --> 00:25:44,515 OKAY. 558 00:25:44,515 --> 00:25:46,483 AND THEN ON TO FUNDS. 559 00:25:46,483 --> 00:25:49,486 SO SOME RESEARCH AND PROGRAM 560 00:25:49,486 --> 00:25:49,787 HIGHLIGHTS. 561 00:25:49,787 --> 00:25:53,524 THERE'S A LOT SO I THOUGHT I'D 562 00:25:53,524 --> 00:25:56,493 JUST SHOW IT AS A SPREAD SHEET. 563 00:25:56,493 --> 00:25:58,729 AND I'M NOT GOING TO GO THROUGH 564 00:25:58,729 --> 00:26:02,766 ALL THESE IN DETAIL. 565 00:26:02,766 --> 00:26:04,735 DIFFERENT PUBLICATIONS AND 566 00:26:04,735 --> 00:26:07,438 INITIATIVES BUT A NEW CRISPR 567 00:26:07,438 --> 00:26:09,707 SCREENING PLATFORM THAT'S 568 00:26:09,707 --> 00:26:11,375 SUCCESSFULLY SHOWN. 569 00:26:11,375 --> 00:26:13,944 PEOPLE BOOST SENSITIVITY. 570 00:26:13,944 --> 00:26:16,747 A NEW WORK IN RAS PARTICULARLY 571 00:26:16,747 --> 00:26:20,150 ON K RAS FOR A VARIANT. 572 00:26:20,150 --> 00:26:21,051 THE SHIFT TRIAL. 573 00:26:21,051 --> 00:26:22,820 WE'RE REALLY EXCITED ABOUT THIS 574 00:26:22,820 --> 00:26:25,122 TRIAL WHICH IS SELF-COLLECTION 575 00:26:25,122 --> 00:26:28,726 OF HPV FOR WOMEN FOR DETECTING 576 00:26:28,726 --> 00:26:30,494 RISK FOR CERVICAL CANCER. 577 00:26:30,494 --> 00:26:34,398 THIS HAS OPENED AND HAS ENROLLED 578 00:26:34,398 --> 00:26:35,632 PATIENTS IN VERY QUICK TIME AND 579 00:26:35,632 --> 00:26:39,136 IS A REALLY EXCITING TRIAL TO 580 00:26:39,136 --> 00:26:40,838 PUT RISK ASSESSMENT LITERALLY 581 00:26:40,838 --> 00:26:42,773 INTO THE HANDS OF PATIENTS AND 582 00:26:42,773 --> 00:26:45,943 MOVE TO A DIFFERENT KIND OF 583 00:26:45,943 --> 00:26:47,945 MENTALITY OF HOW WE ADDRESS RISK 584 00:26:47,945 --> 00:26:50,748 FOR IN THIS CASE CERVICAL 585 00:26:50,748 --> 00:26:51,882 CANCER. 586 00:26:51,882 --> 00:26:54,752 WE'RE ALSO LOOKING AT SOME 587 00:26:54,752 --> 00:26:56,386 REALLY EXCITING WORK ON NEW 588 00:26:56,386 --> 00:26:57,921 INHIBITORS FOR RAS. 589 00:26:57,921 --> 00:27:02,259 I THINK YOU'LL HEAR MORE ABOUT 590 00:27:02,259 --> 00:27:03,060 THAT LATER AND FREDERICK 591 00:27:03,060 --> 00:27:05,562 NATIONAL LAB IS NOT ALL CANCER. 592 00:27:05,562 --> 00:27:09,133 WE'RE THE STEWARDS OF THE 593 00:27:09,133 --> 00:27:09,800 FREDERICK NATIONAL LAB BUT IT'S 594 00:27:09,800 --> 00:27:10,934 A NATIONAL LAB FOR ALL BIO 595 00:27:10,934 --> 00:27:11,401 MEDICAL SCIENCE. 596 00:27:11,401 --> 00:27:13,504 I WANTED TO MAKE SURE YOU WERE 597 00:27:13,504 --> 00:27:19,476 AWARE OF SOME OF THE EXCITING 598 00:27:19,476 --> 00:27:21,879 WORK HAPPENING AROUND WORK 599 00:27:21,879 --> 00:27:23,747 IDENTIFYING ANTIBODIES FOR A 600 00:27:23,747 --> 00:27:29,186 UNIVERSAL FLU VACCINE. 601 00:27:29,186 --> 00:27:32,055 AND IN THE ARENA OF TRANSFORMING 602 00:27:32,055 --> 00:27:34,291 CLINICAL RESEARCH SO THIS SORT 603 00:27:34,291 --> 00:27:38,295 OF COMBINES BY ACR AND ASCO 604 00:27:38,295 --> 00:27:39,329 TALKS AND EVERYONE INCLUDED AND 605 00:27:39,329 --> 00:27:45,135 CAN WE MOVE FORWARD FASTER IS 606 00:27:45,135 --> 00:27:47,004 THE IDEA OF GETTING CLINICAL 607 00:27:47,004 --> 00:27:48,438 TRIALS OUT WHERE THE TRIALS ARE 608 00:27:48,438 --> 00:27:54,378 AND IN THEIR CARE AND PILOTING 609 00:27:54,378 --> 00:27:55,045 VIRTUAL CLINICAL TRIALS AND 610 00:27:55,045 --> 00:27:55,679 FREDERICK NATIONAL LAB IS AN 611 00:27:55,679 --> 00:27:58,448 IMPORTANT PART OF THIS TO BRING 612 00:27:58,448 --> 00:28:00,017 THE STAFFING THAT'S REQUIRED TO 613 00:28:00,017 --> 00:28:02,753 DO CLINICAL WORK OUT INTO SPACES 614 00:28:02,753 --> 00:28:03,987 THROUGH VIRTUAL MEETS AND THIS 615 00:28:03,987 --> 00:28:06,757 IS 2024. 616 00:28:06,757 --> 00:28:12,830 THIS IS WORK WE'RE LEARNING HOW 617 00:28:12,830 --> 00:28:15,199 TO DO THAT AND THE CLINICAL 618 00:28:15,199 --> 00:28:17,401 TRIAL INNOVATION IS STREAMLINING 619 00:28:17,401 --> 00:28:18,769 CLINICAL TRIALS SO THEY CAN BE 620 00:28:18,769 --> 00:28:22,739 OPEN AND ENROLLED MUCH MORE 621 00:28:22,739 --> 00:28:26,143 QUICKLY. 622 00:28:26,143 --> 00:28:27,344 THE MATCH SUCCESSOR LEANS ON THE 623 00:28:27,344 --> 00:28:30,247 STUDY AND IT WAS A PARADIGM FOR 624 00:28:30,247 --> 00:28:33,083 HOW YOU APPROACH A PATIENT'S 625 00:28:33,083 --> 00:28:37,354 THERAPEUTIC DECISION MAKING. 626 00:28:37,354 --> 00:28:38,722 SO MYELOMATCH IS OPEN AND I 627 00:28:38,722 --> 00:28:42,259 THINK ENROLLED THE FIRST 628 00:28:42,259 --> 00:28:42,492 PATIENT. 629 00:28:42,492 --> 00:28:46,730 COMBO AND IMMUNOMATCH ARE BOTH 630 00:28:46,730 --> 00:28:47,030 ON THE WAY. 631 00:28:47,030 --> 00:28:49,266 AND WORKING BROADLY ACROSS THE 632 00:28:49,266 --> 00:28:50,567 CLINICAL RESEARCH SPACE AND A 633 00:28:50,567 --> 00:28:51,802 SHUT OUT THAT WE HAVE A WORKING 634 00:28:51,802 --> 00:28:56,440 GROUP LOOKING AT ENHANCING 635 00:28:56,440 --> 00:28:58,175 CANCER RESEARCH AND QUALITY 636 00:28:58,175 --> 00:28:58,475 CARE. 637 00:28:58,475 --> 00:29:00,544 LOOKING AT HOW DO WE GET 638 00:29:00,544 --> 00:29:01,778 CAPACITY BUILT OUTSIDE OF THE 639 00:29:01,778 --> 00:29:04,548 MAJOR ACADEMIC CENTERS. 640 00:29:04,548 --> 00:29:05,215 BECAUSE THAT'S WHERE MOST 641 00:29:05,215 --> 00:29:09,786 PATIENTS ARE GETTING THEIR CARE. 642 00:29:09,786 --> 00:29:12,823 AND IT FEEDS WELL INTO THIS 643 00:29:12,823 --> 00:29:15,425 WHICH IS THE PART OF THE CANCER 644 00:29:15,425 --> 00:29:17,961 MOONSHOT THE CREATION CANCER 645 00:29:17,961 --> 00:29:18,328 CABINET. 646 00:29:18,328 --> 00:29:19,830 THE CABINET FOR THE FIRST TIME 647 00:29:19,830 --> 00:29:22,733 IS HOSTING A SERIES OF COMMUNITY 648 00:29:22,733 --> 00:29:23,233 CONVERSATIONS. 649 00:29:23,233 --> 00:29:24,735 THESE ARE WEB-BASED 650 00:29:24,735 --> 00:29:26,203 OPPORTUNITIES FOR COMMUNITY TO 651 00:29:26,203 --> 00:29:26,870 ENGAGE WITH EXPERTS. 652 00:29:26,870 --> 00:29:30,407 WE HAVE A TOPIC AND OURS IS 653 00:29:30,407 --> 00:29:31,975 GOING ON -- YOU'LL MISS IT 654 00:29:31,975 --> 00:29:33,010 BECAUSE IT'S NOW AND STARTS IN 655 00:29:33,010 --> 00:29:33,443 HALF AN HOUR. 656 00:29:33,443 --> 00:29:36,146 BUT OUR TOPIC IS IMPROVING 657 00:29:36,146 --> 00:29:37,881 CANCER OUTCOMES: BRINGING 658 00:29:37,881 --> 00:29:39,216 RESEARCH TO RURAL COMMUNITIES 659 00:29:39,216 --> 00:29:43,921 BUT THERE ARE TOPICS THROUGHOUT 660 00:29:43,921 --> 00:29:47,357 THE NEXT TWO WEEKS TO GET TO 661 00:29:47,357 --> 00:29:48,492 BRINGING THE INNOVATION AND 662 00:29:48,492 --> 00:29:51,061 EXCITEMENT AND WORK OUT IN THE 663 00:29:51,061 --> 00:30:01,238 COMMUNITY. 664 00:30:03,674 --> 00:30:07,744 FINALLY A SHOWCASE OF TECHNOLOGY 665 00:30:07,744 --> 00:30:09,947 IN SEPTEMBER AND THE ANNUAL RAS 666 00:30:09,947 --> 00:30:14,918 INITIATIVE SYMPOSIUM THE FIFTH 667 00:30:14,918 --> 00:30:17,688 ONE IS IN OCTOBER AND THE WORK 668 00:30:17,688 --> 00:30:25,996 HAS BLOSSOMED BEAUTIFULLY. 669 00:30:25,996 --> 00:30:27,764 THAT GETS ME TO THE NEW HALLMARK 670 00:30:27,764 --> 00:30:30,467 OF WHAT I'M GOING AT THE BOARD 671 00:30:30,467 --> 00:30:31,401 TALKS MAKING SURE WHAT IT IS I 672 00:30:31,401 --> 00:30:32,636 NEED FROM YOU AS BOARD MEMBERS 673 00:30:32,636 --> 00:30:41,178 AND WHAT I NEED FROM YOU WE CAN 674 00:30:41,178 --> 00:30:42,612 TALK ABOUT IN THE NEXT FIVE 675 00:30:42,612 --> 00:30:44,214 MINUTES OR WHENEVER YOU HAVE AN 676 00:30:44,214 --> 00:30:48,352 IDEA BUT HOW CAN WE ACHIEVE THE 677 00:30:48,352 --> 00:30:49,553 GOALS OF THE NATIONAL CANCER 678 00:30:49,553 --> 00:30:50,754 PLAN AND DO WE HAVE THE RESOURCE 679 00:30:50,754 --> 00:30:54,157 TO BUILD THE CAPACITY FOR THE 680 00:30:54,157 --> 00:30:58,261 NATION'S CANCER INITIATIVE. 681 00:30:58,261 --> 00:31:01,665 THAT'S WHAT WE VIEW THIS FOR AND 682 00:31:01,665 --> 00:31:03,266 YOUR INPUTS ARE VALUABLE AND 683 00:31:03,266 --> 00:31:08,405 MAKES US LEVEL SET AND 684 00:31:08,405 --> 00:31:09,806 SUGGESTIONS HOW TO MOVE FORWARD 685 00:31:09,806 --> 00:31:11,008 FASTER ARE WELCOMED. 686 00:31:11,008 --> 00:31:11,441 THANK YOU VERY MUCH. 687 00:31:11,441 --> 00:31:20,784 I'LL STOP THERE. 688 00:31:20,784 --> 00:31:21,885 >> WE HAVE SOME TIME. 689 00:31:21,885 --> 00:31:32,362 A FEW MINUTES FOR QUESTIONS. 690 00:31:32,562 --> 00:31:33,764 YOU'RE MUTED. 691 00:31:33,764 --> 00:31:37,200 >> THANK YOU SO MUCH, KIM. 692 00:31:37,200 --> 00:31:42,005 CONGRATULATIONS ON BEING IN YOUR 693 00:31:42,005 --> 00:31:48,612 ROLE FOR ALMOST A YEAR. 694 00:31:48,612 --> 00:31:49,880 HOW MANY PEOPLE CAME AND WHO 695 00:31:49,880 --> 00:31:52,215 WERE THE MAIN SPEAKERS AND ARE 696 00:31:52,215 --> 00:31:57,587 YOU GOING TO DO IT AGAIN. 697 00:31:57,587 --> 00:31:58,755 >> SO, I SHOULD KNOW THIS NUMBER 698 00:31:58,755 --> 00:32:00,490 OFF THE TOP OF MY HEAD BECAUSE 699 00:32:00,490 --> 00:32:02,125 WE HAD TO MOVE IT AND KEEP 700 00:32:02,125 --> 00:32:03,894 INCREASING THE SPACE BECAUSE 701 00:32:03,894 --> 00:32:05,195 WAITING LIST WOULD FILL UP EVERY 702 00:32:05,195 --> 00:32:05,662 TIME. 703 00:32:05,662 --> 00:32:09,566 I WANT TO SAY IT WAS 500 OR SO 704 00:32:09,566 --> 00:32:10,734 IF THERE'S ANYONE ONLINE WHO 705 00:32:10,734 --> 00:32:12,469 KNOWS THE NUMBER MORE ACCURATELY 706 00:32:12,469 --> 00:32:13,937 THAN ME. 707 00:32:13,937 --> 00:32:14,538 PLEASE LET ME KNOW. 708 00:32:14,538 --> 00:32:17,107 THAT'S WHAT IT LOOKED LIKE WHEN 709 00:32:17,107 --> 00:32:20,010 I WAS TALKING. 710 00:32:20,010 --> 00:32:24,381 THE AUDIENCE WAS A MIX OF 711 00:32:24,381 --> 00:32:26,750 TRAINEES AND MORE SENIOR 712 00:32:26,750 --> 00:32:32,556 INVESTIGATORS, CLINICAL, BASIC. 713 00:32:32,556 --> 00:32:36,326 ALL DIFFERENT ASPECTS. 714 00:32:36,326 --> 00:32:41,698 THE TALKS WERE ON A RANGE OF 715 00:32:41,698 --> 00:32:45,368 CAREER DEVELOPMENT, SCIENCE 716 00:32:45,368 --> 00:32:47,704 WHERE THERE'S ACTUALLY THE TALK 717 00:32:47,704 --> 00:32:52,676 I REALLY ENJOYED MOST WAS FROM 718 00:32:52,676 --> 00:32:53,677 THE NEW CANCER GRANT CHALLENGES 719 00:32:53,677 --> 00:32:57,514 PROGRAM. 720 00:32:57,514 --> 00:33:04,020 IT'S LOOKING AT ANCESTRY AND 721 00:33:04,020 --> 00:33:06,490 RISK FOR CANCER AND REALLY 722 00:33:06,490 --> 00:33:06,823 POWERFUL TALK. 723 00:33:06,823 --> 00:33:09,960 IT WAS THAT KIND OF TALK AND IT 724 00:33:09,960 --> 00:33:12,129 WAS GOOD AND I HOPE THEY DO IT 725 00:33:12,129 --> 00:33:12,429 AGAIN. 726 00:33:12,429 --> 00:33:14,731 I THINK IT WAS WELL ENOUGH 727 00:33:14,731 --> 00:33:16,399 RECEIVED I WOULD ASSUME SO BUT I 728 00:33:16,399 --> 00:33:21,805 DON'T KNOW THE DETAILS. 729 00:33:21,805 --> 00:33:22,973 >> YES, BLOSSOM. 730 00:33:22,973 --> 00:33:24,174 >> HI, KIM. 731 00:33:24,174 --> 00:33:24,875 THANK YOU FOR THE PRECIPITATION. 732 00:33:24,875 --> 00:33:27,544 YOU MAY NOT BE ABLE TO SPEAK 733 00:33:27,544 --> 00:33:29,513 ABOUT THIS BUT I WAS WONDERING 734 00:33:29,513 --> 00:33:34,751 IF YOU HAD ANY THOUGHTS ON THE 735 00:33:34,751 --> 00:33:38,088 NEW PROPOSAL TO INFORM AND HOW 736 00:33:38,088 --> 00:33:38,889 IT WILL IMPACT NCI? 737 00:33:38,889 --> 00:33:41,391 >> SO, I PROBABLY CAN'T SAY A 738 00:33:41,391 --> 00:33:44,227 LOT BECAUSE I DON'T KNOW MORE 739 00:33:44,227 --> 00:33:49,833 THAN YOU ALL KNOW WHAT'S IN THE 740 00:33:49,833 --> 00:33:50,400 PRESS. 741 00:33:50,400 --> 00:33:53,436 IT'S NICE TO SEE CANCER WASN'T 742 00:33:53,436 --> 00:33:53,737 REORGANIZED. 743 00:33:53,737 --> 00:33:56,306 SO I THINK PEOPLE UNDERSTAND AND 744 00:33:56,306 --> 00:33:58,141 APPRECIATE CANCER IN A DIFFERENT 745 00:33:58,141 --> 00:34:04,147 WAY THAN THEY CAN OTHER DISEASES 746 00:34:04,147 --> 00:34:06,750 AND I THINK THERE'S VALUE IN ALL 747 00:34:06,750 --> 00:34:08,251 THE NIH. 748 00:34:08,251 --> 00:34:11,121 SO WE'RE WATCHING ALL THIS AS 749 00:34:11,121 --> 00:34:11,321 WELL. 750 00:34:11,321 --> 00:34:15,091 >> THANKS. 751 00:34:15,091 --> 00:34:20,030 >> JOHN IS HAVING ISSUES WITH 752 00:34:20,030 --> 00:34:22,766 HIS MICROPHONE. 753 00:34:22,766 --> 00:34:30,173 JOHN. 754 00:34:30,173 --> 00:34:36,146 >> I HAVE THE QUESTION THAT BLUE 755 00:34:36,146 --> 00:34:37,280 -- BLEW OFF MY PAGE. 756 00:34:37,280 --> 00:34:38,748 >> THERE WAS A LIST OF SPEAKERS. 757 00:34:38,748 --> 00:34:42,752 >> THERE WAS A QUESTION FROM 758 00:34:42,752 --> 00:34:43,153 JOHN. 759 00:34:43,153 --> 00:34:43,887 JOHN'S QUESTION WAS -- MY 760 00:34:43,887 --> 00:34:46,323 QUESTION IS HOW DO YOU GET THE 761 00:34:46,323 --> 00:34:47,924 FOCUS ON INNOVATION TO PERCOLATE 762 00:34:47,924 --> 00:34:53,730 DOWN TO THE REVIEWERS OF GRANTS 763 00:34:53,730 --> 00:34:56,833 WHERE REVIEWERS VARY WIDELY ON 764 00:34:56,833 --> 00:34:58,768 HOW MUCH VALUE THEY PLACE -- 765 00:34:58,768 --> 00:35:01,972 >> YES, THANKS. 766 00:35:01,972 --> 00:35:03,807 WOW, SOME DAYS I WISH I HAD A 767 00:35:03,807 --> 00:35:06,876 DEGREE IN PSYCHOLOGY. 768 00:35:06,876 --> 00:35:10,247 I THINK WE MAKE IT VERY CLEAR 769 00:35:10,247 --> 00:35:11,715 INNOVATION IS A HUGE PRIORITY. 770 00:35:11,715 --> 00:35:17,721 WE'RE TALKING A LOT ABOUT HOW WE 771 00:35:17,721 --> 00:35:20,056 WRITE OUR REQUESTS SO THAT IT'S 772 00:35:20,056 --> 00:35:25,629 CLEAR WE'RE PRIORITIZING 773 00:35:25,629 --> 00:35:25,929 INNOVATION. 774 00:35:25,929 --> 00:35:27,364 ACTUALLY I'VE BEEN THINKING 775 00:35:27,364 --> 00:35:30,367 ABOUT THIS IN TERMS OF HOW WE 776 00:35:30,367 --> 00:35:32,502 HELP REVIEWERS LEVEL SET WHETHER 777 00:35:32,502 --> 00:35:38,742 IT'S ABOUT PAPERS OR GRANTS AND 778 00:35:38,742 --> 00:35:44,981 WHERE THE APPROPRIATE LEVEL OF 779 00:35:44,981 --> 00:35:50,754 CRITIQUE VERSUS SORT OF OFF THE 780 00:35:50,754 --> 00:35:50,954 MARK. 781 00:35:50,954 --> 00:35:53,757 THAT'S A HARD ONE. 782 00:35:53,757 --> 00:35:58,762 I AGREE. 783 00:35:58,762 --> 00:35:59,095 >> THANK YOU. 784 00:35:59,095 --> 00:36:01,097 SO DR. RATHMELL I WANT TO 785 00:36:01,097 --> 00:36:03,600 CONGRATULATE YOU ON YOUR 786 00:36:03,600 --> 00:36:05,468 ACCOMPLISHMENT TO DATE. 787 00:36:05,468 --> 00:36:07,304 MY QUESTION IS WITH REGARD TO 788 00:36:07,304 --> 00:36:08,438 THE COMMENT ON THE LAST SLIDE 789 00:36:08,438 --> 00:36:10,740 WITH REGARD TO CAPACITY AND 790 00:36:10,740 --> 00:36:11,274 INFRASTRUCTURE. 791 00:36:11,274 --> 00:36:16,179 I WONDERED -- THIS IS NOT A NEW 792 00:36:16,179 --> 00:36:18,782 QUESTION SO EXCUSE ME IF I SOUND 793 00:36:18,782 --> 00:36:22,719 LIKE A BROKEN RECORD BUT WHAT IF 794 00:36:22,719 --> 00:36:23,586 ANYTHING IS HAPPENING WITH 795 00:36:23,586 --> 00:36:28,358 REGARD TO LEVERAGING THE HUGE 796 00:36:28,358 --> 00:36:30,627 AMOUNT OF DATA WITHIN OUR WORLD 797 00:36:30,627 --> 00:36:33,463 AND MAKING THAT AVAILABLE AS A 798 00:36:33,463 --> 00:36:40,437 RESOURCE FOR OUR TRAINING A.I. 799 00:36:40,437 --> 00:36:42,272 ALGORITHMS FOR PROGNOSTIC ASSAYS 800 00:36:42,272 --> 00:36:43,573 FOR IDENTIFYING PATIENTS THAT 801 00:36:43,573 --> 00:36:46,209 WILL BENEFIT FROM SOME OF THESE 802 00:36:46,209 --> 00:36:47,777 THERAPIES AND ALTERNATIVELY ALSO 803 00:36:47,777 --> 00:36:49,279 THE HUGE OPPORTUNITY POTENTIALLY 804 00:36:49,279 --> 00:36:50,947 WITH THESE ALGORITHMS FOR 805 00:36:50,947 --> 00:36:53,350 LOOKING AT NEGATIVE TRIALS AND 806 00:36:53,350 --> 00:36:58,855 POTENTIALLY RESUSCITATING SOME 807 00:36:58,855 --> 00:36:59,756 OF THESE TRIALS. 808 00:36:59,756 --> 00:37:01,591 >> SO, PLEASE FEEL FREE TO KEEP 809 00:37:01,591 --> 00:37:02,692 ASKING THAT QUESTION UNTIL WE 810 00:37:02,692 --> 00:37:03,526 GET IT RIGHT. 811 00:37:03,526 --> 00:37:05,462 I THINK WE'RE INTERESTED IN 812 00:37:05,462 --> 00:37:06,863 MAKING DATA AVAILABLE AND BEING 813 00:37:06,863 --> 00:37:08,298 ABLE TO SHARE IT TO ANSWER THE 814 00:37:08,298 --> 00:37:10,734 QUESTIONS AND DEFINITELY NOT 815 00:37:10,734 --> 00:37:12,902 DUPLICATE WORK AND DEFINITELY -- 816 00:37:12,902 --> 00:37:14,771 THIS IS WHERE WE'RE IN A TIGHT 817 00:37:14,771 --> 00:37:15,939 BUDGET LIKE THIS FOR A LONG 818 00:37:15,939 --> 00:37:17,774 PERIOD OF TIME WE CAN'T AFFORD 819 00:37:17,774 --> 00:37:23,179 TO DO THAT. 820 00:37:23,179 --> 00:37:30,754 THIS IS WHERE HAVING DR. KIBBE 821 00:37:30,754 --> 00:37:32,389 ON BOARD WILL BE HELPFUL AND HOW 822 00:37:32,389 --> 00:37:33,656 BEST TO DO THAT AND THAT'S ALL I 823 00:37:33,656 --> 00:37:34,190 CAN SAY ABOUT THAT AT THE 824 00:37:34,190 --> 00:37:41,798 MOMENT. 825 00:37:41,798 --> 00:37:46,603 >> SO WE'RE RUNNING A LITTLE 826 00:37:46,603 --> 00:37:48,304 LATE SO TWO MORE QUESTIONS. 827 00:37:48,304 --> 00:37:48,972 >> I CAN'T THANK YOU ENOUGH FOR 828 00:37:48,972 --> 00:37:50,673 DOING WHAT YOU DO BECAUSE IT'S A 829 00:37:50,673 --> 00:37:52,242 HARD JOB AND WE ALL APPRECIATE 830 00:37:52,242 --> 00:37:54,644 IT IMMENSELY. 831 00:37:54,644 --> 00:37:57,180 ONE THING YOU SAID BOTHERS ME A 832 00:37:57,180 --> 00:38:01,418 BIT HOW TO WE PUT RESOURCES INTO 833 00:38:01,418 --> 00:38:02,452 FREDERICK TO BUILD WHAT WE NEED. 834 00:38:02,452 --> 00:38:04,521 IT OCCURS DO ME WE DON'T HAVE TO 835 00:38:04,521 --> 00:38:06,122 BUILD EVERYTHING AT FREDERICK. 836 00:38:06,122 --> 00:38:08,858 WE CAN TAKE ADVANTAGE OF THE 837 00:38:08,858 --> 00:38:12,228 NATIONAL CANCER CENTERS AND 838 00:38:12,228 --> 00:38:13,797 PERHAPS ISSUE RFPs FOR THE 839 00:38:13,797 --> 00:38:17,400 CANCER CENTERS TO PROVIDE THE 840 00:38:17,400 --> 00:38:20,236 METHODOLOGY THAT MAY ALREADY BE 841 00:38:20,236 --> 00:38:20,804 BUILT WITHIN THEIR VARIOUS 842 00:38:20,804 --> 00:38:22,338 INSTITUTIONS. 843 00:38:22,338 --> 00:38:24,641 AND THAT WOULD NOT ONLY SAVE US 844 00:38:24,641 --> 00:38:26,176 FUNDING BUT IT WOULD PROBABLY 845 00:38:26,176 --> 00:38:29,579 GET US TO THE GOAL FASTER. 846 00:38:29,579 --> 00:38:33,716 >> YEAH, I LOVE THAT AND THAT 847 00:38:33,716 --> 00:38:37,420 ALSO IS SPEAKING TO CREATING 848 00:38:37,420 --> 00:38:41,024 MORE OF A NETWORK AND NOT HAVING 849 00:38:41,024 --> 00:38:42,258 THIS BE A HUB EVERYONE NEEDS TO 850 00:38:42,258 --> 00:38:45,328 COME TO AND I AGREE COMPLETELY. 851 00:38:45,328 --> 00:38:48,598 >> ALSO TO PLAY ON THE LAST 852 00:38:48,598 --> 00:38:50,533 SEVERAL COMMENTS AND REVIEWERS 853 00:38:50,533 --> 00:38:51,868 CRITICIZING GRANTS ESPECIALLY 854 00:38:51,868 --> 00:38:57,407 FOR THE YOUNG ADVOCINVESTIGATOR. 855 00:38:57,407 --> 00:38:58,541 MY EXPERIENCE OF REVIEW 856 00:38:58,541 --> 00:38:59,809 COMMITTEES IS THEY'RE RISK 857 00:38:59,809 --> 00:39:01,277 AVERSE AND DON'T GET THEY'RE 858 00:39:01,277 --> 00:39:02,145 RISK WITH THE YOUNG 859 00:39:02,145 --> 00:39:04,881 INVESTIGATORS AND INNOVATION 860 00:39:04,881 --> 00:39:06,149 MEANS SOMETHING LIKELY DIFFERENT 861 00:39:06,149 --> 00:39:07,550 FROM THEM THAN WHAT IT MEANS TO 862 00:39:07,550 --> 00:39:09,319 ALL OF US OLD DOGS. 863 00:39:09,319 --> 00:39:10,753 I WOULD ENCOURAGE SOME EDUCATION 864 00:39:10,753 --> 00:39:13,323 TO GO INTO THE REVIEW COMMITTEES 865 00:39:13,323 --> 00:39:15,225 BEFORE THEY MEET AND GET THEIR 866 00:39:15,225 --> 00:39:15,492 GRANTS. 867 00:39:15,492 --> 00:39:17,260 BECAUSE THEY NEED TO START 868 00:39:17,260 --> 00:39:17,861 REVIEWING GRANTS WITH A 869 00:39:17,861 --> 00:39:24,234 DIFFERENT EYE. 870 00:39:24,234 --> 00:39:25,835 >> CAROL, OUR LAST QUESTION 871 00:39:25,835 --> 00:39:27,103 BEFORE WE MOVE ON. 872 00:39:27,103 --> 00:39:33,209 >> MORE A COMMENT BUILDING ON 873 00:39:33,209 --> 00:39:34,677 PRIOR COMMENTS. 874 00:39:34,677 --> 00:39:35,345 I THINK FREDERICK NATIONAL LAB 875 00:39:35,345 --> 00:39:38,748 COULD BE A POINT OF NUCLEATION 876 00:39:38,748 --> 00:39:40,183 FOR EFFORTS FOR EXTERNAL GROUPS 877 00:39:40,183 --> 00:39:41,251 AS WELL AS INTERNAL. 878 00:39:41,251 --> 00:39:42,919 TO LISA'S POINT YOU DON'T HAVE 879 00:39:42,919 --> 00:39:43,786 TO BUILD EVERYTHING BUT 880 00:39:43,786 --> 00:39:45,989 FREDERICK HAS A REALLY IMPORTANT 881 00:39:45,989 --> 00:39:51,294 ROLE I THINK IN NUCLEATING 882 00:39:51,294 --> 00:39:52,795 FOCUSSED EFFORTS AND BRINGING IN 883 00:39:52,795 --> 00:39:54,731 INVESTIGATORS FROM ALL PARTS TO 884 00:39:54,731 --> 00:39:57,300 WORK COLLABORATIVELY ON 885 00:39:57,300 --> 00:39:57,700 PROJECTS. 886 00:39:57,700 --> 00:40:02,505 I THINK OF AND I THINK FOR DATA 887 00:40:02,505 --> 00:40:03,540 SCIENCE WARREN'S AN EXCELLENT 888 00:40:03,540 --> 00:40:03,873 LEADER. 889 00:40:03,873 --> 00:40:05,575 HE'S A COMMUNITY BUILDER AND 890 00:40:05,575 --> 00:40:07,610 WILL BE GREAT FOR DOING THAT. 891 00:40:07,610 --> 00:40:10,713 I THINK FOR EFFORT LIKE PDX NET, 892 00:40:10,713 --> 00:40:14,651 FREDERICK HAS PLAYED A REALLY 893 00:40:14,651 --> 00:40:15,285 IMPORTANT NUCLEATING ROLE IN 894 00:40:15,285 --> 00:40:16,185 EFFORTS OF THAT INITIATIVE AND 895 00:40:16,185 --> 00:40:22,058 MORE OF THAT I THINK IS WHAT 896 00:40:22,058 --> 00:40:22,659 FREDERICK COULD DO VERY WELL. 897 00:40:22,659 --> 00:40:27,964 >> GREAT, THANK YOU. 898 00:40:27,964 --> 00:40:28,831 OKAY, THANK YOU, KIM. 899 00:40:28,831 --> 00:40:30,466 >> BEFORE I SIGN OFF BECAUSE 900 00:40:30,466 --> 00:40:34,737 WE'RE ON CAMERA, I WANTED TO 901 00:40:34,737 --> 00:40:36,439 MAKE A CORRECTION ABOUT BLACK IN 902 00:40:36,439 --> 00:40:37,740 CANCER. 903 00:40:37,740 --> 00:40:39,208 APPARENTLY THIS IS THE FIRST IN 904 00:40:39,208 --> 00:40:40,643 NORTH AMERICA. 905 00:40:40,643 --> 00:40:43,146 THIS WAS ONE IN 2022 IN LONDON. 906 00:40:43,146 --> 00:40:44,347 WITH THAT CORRECTION AND 907 00:40:44,347 --> 00:40:46,749 HOPEFULLY WE'LL ALTERNATE BACK 908 00:40:46,749 --> 00:40:47,016 AND FORTH. 909 00:40:47,016 --> 00:40:47,850 >> THANK YOU SO MUCH. 910 00:40:47,850 --> 00:40:48,985 THANK YOU. 911 00:40:48,985 --> 00:40:51,788 >> NOW WE'RE GOING TO TURN TO 912 00:40:51,788 --> 00:40:55,792 DR. KARLOVICH WHO WILL TALK TO 913 00:40:55,792 --> 00:40:58,161 US ABOUT FNLAC SUPPORT FRIENDS 914 00:40:58,161 --> 00:41:02,732 OF CANCER RESEARCH TUMOR 915 00:41:02,732 --> 00:41:13,276 MUTATIONAL BURDEN AND HOMOLOGOUS 916 00:41:14,410 --> 00:41:14,944 RECOMBINATION DEFICIENCY FOR 917 00:41:14,944 --> 00:41:21,317 HARMONIZATION PROJECTS. 918 00:41:21,317 --> 00:41:31,394 IT 919 00:42:00,156 --> 00:42:03,926 >> CAN YOU HEAR ME NOW. 920 00:42:03,926 --> 00:42:05,728 SORRY, I WAS HAVING TROUBLE 921 00:42:05,728 --> 00:42:06,129 UNMUTING MYSELF. 922 00:42:06,129 --> 00:42:09,966 GOOD AFTERNOON, EVERYBODY. 923 00:42:09,966 --> 00:42:11,567 THANK YOU FOR JOINING TODAY. 924 00:42:11,567 --> 00:42:14,737 I'M SHARING MY SLIDES HOPEFULLY 925 00:42:14,737 --> 00:42:25,148 EVERYBODY CAN SEE THOSE. 926 00:42:34,524 --> 00:42:35,525 AND I'LL TALK ABOUT TWO PROJECTS 927 00:42:35,525 --> 00:42:35,858 TODAY. 928 00:42:35,858 --> 00:42:40,229 THE FIRST IS AN EFFORT TO 929 00:42:40,229 --> 00:42:40,797 HARMONIZE TUMOR MUTATIONAL 930 00:42:40,797 --> 00:42:41,030 BURDEN. 931 00:42:41,030 --> 00:42:42,699 THAT PROJECT WAS INITIATED IN 932 00:42:42,699 --> 00:42:45,268 THE FALL OF 2017 AND RAN FOR 933 00:42:45,268 --> 00:42:46,769 THREE YEARS AND ALL THE DATA'S 934 00:42:46,769 --> 00:42:48,204 BEEN PUBLISHED. 935 00:42:48,204 --> 00:42:50,740 THEN I'LL TALK MORE RECENTLY NOW 936 00:42:50,740 --> 00:42:52,975 ABOUT A PROJECT THAT WE'VE BEEN 937 00:42:52,975 --> 00:42:55,778 WORKING ON AND IS JUST WRAPPING 938 00:42:55,778 --> 00:43:00,583 UP TO HARMONIZE CONFLICTS BOUND 939 00:43:00,583 --> 00:43:01,217 MARKER FROM HOMOLOGOUS 940 00:43:01,217 --> 00:43:01,751 RECOMBINATION DEFICIENCY. 941 00:43:01,751 --> 00:43:03,886 I WANT TO MAKE SURE AT THE 942 00:43:03,886 --> 00:43:08,424 BEGINNING I GIVE SPECIAL THANKS 943 00:43:08,424 --> 00:43:16,566 TO LISA McSHANE A STATISTICIAN 944 00:43:16,566 --> 00:43:22,004 AND MICKY WILLIAMS WIHO RETIRED 945 00:43:22,004 --> 00:43:24,507 WHO PLAYED AN IMPORTANT ROLE IN 946 00:43:24,507 --> 00:43:26,409 THE TMB PROJECT. 947 00:43:26,409 --> 00:43:28,211 I THINK EVERYBODY ON THE CALL IS 948 00:43:28,211 --> 00:43:31,214 FAMILIAR WITH TMB. 949 00:43:31,214 --> 00:43:34,083 IT'S THE NUMBER OF SOMATIC 950 00:43:34,083 --> 00:43:37,186 MUTATIONS IN GENOME PER MEGA 951 00:43:37,186 --> 00:43:37,386 BASE. 952 00:43:37,386 --> 00:43:42,825 YOU SEE IT IN NUMEROUS TUMOR 953 00:43:42,825 --> 00:43:48,030 TYPES AND A SURROGATE FOR 954 00:43:48,030 --> 00:43:49,465 NEOANTIGEN LOAD AS ALL ON THE 955 00:43:49,465 --> 00:43:53,536 CALL ARE PROBABLY AWARE AND IS A 956 00:43:53,536 --> 00:43:54,737 PREDICTIVE BIOMEDICAL FOR 957 00:43:54,737 --> 00:43:57,406 RESPONSE TO CHECKPOINT BLOCKADE. 958 00:43:57,406 --> 00:44:00,176 THE PROBLEM AND CHALLENGE IS 959 00:44:00,176 --> 00:44:04,714 THAT METHODS FOR ESTIMATING TMB 960 00:44:04,714 --> 00:44:06,449 VARY WIDELY ACROSS CLINICAL 961 00:44:06,449 --> 00:44:06,682 STUDIES. 962 00:44:06,682 --> 00:44:08,551 TO ADDRESS THIS CHALLENGE, 963 00:44:08,551 --> 00:44:09,886 FRIENDS OF CANCER RESEARCH DID 964 00:44:09,886 --> 00:44:10,787 WHAT THEY DO BEST. 965 00:44:10,787 --> 00:44:15,758 THEY PUT TOGETHER A 966 00:44:15,758 --> 00:44:18,795 PUBLIC-PRIVATE CONSORTIUM 967 00:44:18,795 --> 00:44:23,132 CONSISTING OF FDA, NCI, 968 00:44:23,132 --> 00:44:23,699 FREDERICK NATIONAL LAB AND 969 00:44:23,699 --> 00:44:24,367 DERIVATIVE STAKEHOLDERS TO TRY 970 00:44:24,367 --> 00:44:26,736 TO CONDUCT STUDIES TO GENERATE 971 00:44:26,736 --> 00:44:29,172 EVIDENCE THAT MIGHT DRIVE 972 00:44:29,172 --> 00:44:29,906 ALIGNMENT AROUND HOW WE ASSESS 973 00:44:29,906 --> 00:44:32,842 TMB. 974 00:44:32,842 --> 00:44:34,744 AND THE PROJECT CONSISTED YOU 975 00:44:34,744 --> 00:44:40,449 SEE HERE OF THREE PHASES. 976 00:44:40,449 --> 00:44:46,722 THE FIRST PHASE THERE WAS WILL 977 00:44:46,722 --> 00:44:48,658 INSILICO ANALYSIS OF TCGA DATA 978 00:44:48,658 --> 00:44:52,261 AND IN THE LAST PHASES WE DID 979 00:44:52,261 --> 00:44:54,397 WET LAB WORK ON CELL LINES AND 980 00:44:54,397 --> 00:44:57,934 CLINICAL SAMPLES. 981 00:44:57,934 --> 00:45:08,477 I'LL START WITH DATA FROM THE IN 982 00:45:13,983 --> 00:45:15,751 SILICO FACE FROM LABORATORIES 983 00:45:15,751 --> 00:45:17,486 THAT ARE ALL HOUSEHOLD NAMES. 984 00:45:17,486 --> 00:45:18,387 I'M SURE YOU'RE FAMILIAR WITH 985 00:45:18,387 --> 00:45:21,290 MANY AND I WANTED TO TAKE ABOUT 986 00:45:21,290 --> 00:45:24,827 THEY'RE ASSAYS AND ALL THE LABS 987 00:45:24,827 --> 00:45:29,265 ARE TARGETED ON NEXT GENERATION 988 00:45:29,265 --> 00:45:31,567 SEQUENCING PANELS AND THEY VARY 989 00:45:31,567 --> 00:45:38,140 IN SIZE FROM 324 GENES TO 607. 990 00:45:38,140 --> 00:45:41,844 THEY COVER REGIONS OF THE EXOME 991 00:45:41,844 --> 00:45:43,880 AND THE CANCER RELATED GENES 992 00:45:43,880 --> 00:45:50,086 VARIED FROM 800 KILO BASES TO 993 00:45:50,086 --> 00:45:51,587 1.7 MEGABASES. 994 00:45:51,587 --> 00:45:53,389 THAT'S IMPORTANT BECAUSE YOU 995 00:45:53,389 --> 00:45:55,825 NEED A CERTAIN MINIMUM AMOUNT OF 996 00:45:55,825 --> 00:45:59,962 COVERED TO BE ABLE TO GENERATE 997 00:45:59,962 --> 00:46:05,268 BETWEEN 500 KILOBASES AND A MEGA 998 00:46:05,268 --> 00:46:05,635 THERE IS BASE. 999 00:46:05,635 --> 00:46:06,369 ANOTHER FEATURE THAT'S IMPORTANT 1000 00:46:06,369 --> 00:46:09,238 TO CALL OUT AT THE BEGINNING IS 1001 00:46:09,238 --> 00:46:11,974 HOW TMB IS ESTIMATED. 1002 00:46:11,974 --> 00:46:16,312 EVERY LAB USES NON-SYNONYMOUS 1003 00:46:16,312 --> 00:46:17,980 VARIANTS IN THEIR CALCULATION OF 1004 00:46:17,980 --> 00:46:22,718 TMB AND THAT MAKES SENSE BECAUSE 1005 00:46:22,718 --> 00:46:26,722 NON-SYNONYMOUS VARIANTS GIVE 1006 00:46:26,722 --> 00:46:37,300 RISE TO THE -- NEOANTIGENS ONE 1007 00:46:38,834 --> 00:46:41,237 OF THE PARTICIPANTS HAS AN FDA 1008 00:46:41,237 --> 00:46:46,742 APPROVED TEST FOR TMB IT'S TUMOR 1009 00:46:46,742 --> 00:46:51,414 AGNOSTIC. 1010 00:46:51,414 --> 00:46:53,683 AND THERE WERE TWO OTHER 1011 00:46:53,683 --> 00:46:54,016 PARTICIPANTS. 1012 00:46:54,016 --> 00:47:04,260 SORRY MY PRESENTATION IS MOVING. 1013 00:47:04,260 --> 00:47:07,129 IT AND THERE'S TWO OTHERS 1014 00:47:07,129 --> 00:47:08,497 KETTERING AND PERSONAL GENOME 1015 00:47:08,497 --> 00:47:09,265 DIAGNOSTICS. 1016 00:47:09,265 --> 00:47:12,068 I WANT TO SAY A LITTLE BIT ABOUT 1017 00:47:12,068 --> 00:47:14,737 WHAT WE USED RIGHT UP FRONT. 1018 00:47:14,737 --> 00:47:16,305 I MENTIONED THERE WAS AN IN 1019 00:47:16,305 --> 00:47:19,141 SILICO PHASE AND WE LOOKED AT 1020 00:47:19,141 --> 00:47:25,014 OVER 4,000 SAMPLES AND HAD A WET 1021 00:47:25,014 --> 00:47:27,216 LAB PHASE WITH CLINICAL SAMPLES 1022 00:47:27,216 --> 00:47:29,986 AND AGREED AT THE BEGINNING ON A 1023 00:47:29,986 --> 00:47:32,021 GOLD STANDARD BASED ON WHOLE 1024 00:47:32,021 --> 00:47:33,389 EXOME SEQUENCING. 1025 00:47:33,389 --> 00:47:37,293 WE WOULD GENERATE A GOLD 1026 00:47:37,293 --> 00:47:38,427 STANDARD WHOLE EXOME SEQUENCING 1027 00:47:38,427 --> 00:47:41,864 SCORE AND AGREED ON THE METRIC 1028 00:47:41,864 --> 00:47:43,833 IN TERMS OF DEPTH AND ALLELE 1029 00:47:43,833 --> 00:47:46,202 FREQUENCY AND THRESHOLDS. 1030 00:47:46,202 --> 00:47:51,774 WE ALSO AGREED THE DATA WOULD BE 1031 00:47:51,774 --> 00:47:56,145 A MATCHED TUMOR AND GERM LINE 1032 00:47:56,145 --> 00:47:58,647 WHOLE EXOME SEQUENCE TO 1033 00:47:58,647 --> 00:47:59,281 DEFINITIVELY FILTER THE GERM 1034 00:47:59,281 --> 00:48:00,483 LINE VARIANTS AND THE OTHER 1035 00:48:00,483 --> 00:48:02,385 THING THAT WAS IMPORTANT WE 1036 00:48:02,385 --> 00:48:03,686 AGREED UPON WAS WE WOULD ONLY 1037 00:48:03,686 --> 00:48:06,022 INCLUDE NON-SYNONYMOUS VARIANTS 1038 00:48:06,022 --> 00:48:07,890 IN THE CALCULATION OF THE GOLD 1039 00:48:07,890 --> 00:48:11,260 STANDARD WEST TMB. 1040 00:48:11,260 --> 00:48:13,929 FOR EVERY SAMPLE EACH 1041 00:48:13,929 --> 00:48:15,131 PARTICIPANT CALCULATED THEIR 1042 00:48:15,131 --> 00:48:17,933 ONLY PANEL TMB SCORE AND DID A 1043 00:48:17,933 --> 00:48:23,139 PAIR WISE COMPARISON FOR EACH 1044 00:48:23,139 --> 00:48:26,742 LAB AND COMPARED THE LEFT 1045 00:48:26,742 --> 00:48:33,249 STANDARD AND FIT REGRESSION 1046 00:48:33,249 --> 00:48:35,851 LINES IF THE PANEL WILL TMB 1047 00:48:35,851 --> 00:48:37,053 SCORE MATCHED THE GOLD STANDARD 1048 00:48:37,053 --> 00:48:38,554 SCORE THE REGRESSION LINE WOULD 1049 00:48:38,554 --> 00:48:41,624 FALL ALONG THIS DOTTED BLACK 1050 00:48:41,624 --> 00:48:42,725 LINE HERE. 1051 00:48:42,725 --> 00:48:45,795 THAT IS THE IDENTITY LINE. 1052 00:48:45,795 --> 00:48:47,363 AS YOU'LL SEE IN SOME CASES 1053 00:48:47,363 --> 00:48:49,131 WE'RE VERY CLOSE TO THE IDENTITY 1054 00:48:49,131 --> 00:48:51,233 LINE AND IN OTHER CASES WE'RE 1055 00:48:51,233 --> 00:48:53,069 ACTUALLY QUITE FAR AWAY FROM 1056 00:48:53,069 --> 00:48:55,838 THAT IDENTITY LINE. 1057 00:48:55,838 --> 00:49:02,611 AND HERE IS THE IN SILICO AND 1058 00:49:02,611 --> 00:49:06,415 ALL TCGA SAMPLES EXCEPT FOR 1059 00:49:06,415 --> 00:49:13,122 THOSE THAT HAVE A TMB HIGHER 1060 00:49:13,122 --> 00:49:16,425 THAN 40. 1061 00:49:16,425 --> 00:49:19,361 AND WE DECIDED TO RESTRICT THE 1062 00:49:19,361 --> 00:49:23,866 ANALYSIS TO 40 AND LESS BECAUSE 1063 00:49:23,866 --> 00:49:26,335 WE AND THIS REPRESENTS 32 TUMOR 1064 00:49:26,335 --> 00:49:30,039 TIMES AND RIGHT OFF THE BAT WHAT 1065 00:49:30,039 --> 00:49:32,141 YOU'RE PROBABLY SEEING HERE IS 1066 00:49:32,141 --> 00:49:36,011 EIGHT FROM THE 11 LABS HAVE 1067 00:49:36,011 --> 00:49:36,645 REGRESSION LINES WITH SLOPES 1068 00:49:36,645 --> 00:49:37,613 GREATER THAN 1. 1069 00:49:37,613 --> 00:49:41,150 THAT MEANS THEIR PANELS ARE OVER 1070 00:49:41,150 --> 00:49:42,118 ESTIMATING TMB. 1071 00:49:42,118 --> 00:49:45,788 AND THEN WE THOUGHT, WELL, MAYBE 1072 00:49:45,788 --> 00:49:47,623 THAT'S BECAUSE MOST OF THE 1073 00:49:47,623 --> 00:49:52,528 SAMPLES HAVE PRETTY LOW TMB DOWN 1074 00:49:52,528 --> 00:49:55,531 IN THE ZERO TO 10 RANGE AND 1075 00:49:55,531 --> 00:49:57,566 THERE'S A LOT OF SCATTER DOWN 1076 00:49:57,566 --> 00:49:58,000 THERE. 1077 00:49:58,000 --> 00:50:00,469 LET'S FOCUS ON THE TUMOR TYPES 1078 00:50:00,469 --> 00:50:04,140 WITH A NICE DISTRIBUTION OF TMB 1079 00:50:04,140 --> 00:50:08,244 BETWEEN 0 AND 40 AND THAT'S 1080 00:50:08,244 --> 00:50:09,945 EIGHT TUMOR TIMES ABOUT 800 SAM 1081 00:50:09,945 --> 00:50:13,749 MALLS AND LOOKING AT THAT SUBSET 1082 00:50:13,749 --> 00:50:15,518 YOU SEE A TIGHTER DISTRIBUTION 1083 00:50:15,518 --> 00:50:17,920 BETWEEN THE LABS AND 1084 00:50:17,920 --> 00:50:19,555 INTERESTINGLY YOU SEE THE SLOPES 1085 00:50:19,555 --> 00:50:21,290 CONSISTENTLY SHIFTING DOWN. 1086 00:50:21,290 --> 00:50:22,758 SO THAT DID HELP SOME, I WOULD 1087 00:50:22,758 --> 00:50:24,059 SAY. 1088 00:50:24,059 --> 00:50:26,896 BUT THERE'S STILL SOME BIASES 1089 00:50:26,896 --> 00:50:37,006 HERE. 1090 00:50:43,078 --> 00:50:46,782 I'M HAVING TROUBLE ADVANCING THE 1091 00:50:46,782 --> 00:50:48,050 SHIEDZ. 1092 00:50:48,050 --> 00:50:50,753 -- SLIDES IF WE LOOK AT THE 1093 00:50:50,753 --> 00:50:54,089 EIGHT TUMOR TYPE WE SEE 1094 00:50:54,089 --> 00:50:54,757 INTERDEPENDENT RELATIONSHIPS. 1095 00:50:54,757 --> 00:50:56,492 FOR BLADDER CANCER IT TURNS OUT 1096 00:50:56,492 --> 00:50:59,962 ALL 11 LABS SEEM TO BE OVER 1097 00:50:59,962 --> 00:51:03,165 ESTIMATING WITH THEIR PANELS TMB 1098 00:51:03,165 --> 00:51:05,501 RELATIVE TO WEST BUT BY 1099 00:51:05,501 --> 00:51:10,039 COMPARISON IF YOU LOOK AT LUNG 1100 00:51:10,039 --> 00:51:12,374 ADENO AND SQUAMOUS AND MELANOMA 1101 00:51:12,374 --> 00:51:13,842 THERE IS NOT A TREND TOWARDS 1102 00:51:13,842 --> 00:51:15,744 OVER OR UNDERESTIMATE BEING TMB 1103 00:51:15,744 --> 00:51:17,279 ON THE PANELS. 1104 00:51:17,279 --> 00:51:18,080 IT'S VERY INTERESTING THERE 1105 00:51:18,080 --> 00:51:20,382 COULD BE THAT KIND OF CANCER 1106 00:51:20,382 --> 00:51:25,287 DEPENDENT RELATIONSHIP. 1107 00:51:25,287 --> 00:51:30,092 WILL NOW CAN WE MOVE QUICKLY NOW 1108 00:51:30,092 --> 00:51:33,128 INTO THE CLINICAL DATA IN THIS 1109 00:51:33,128 --> 00:51:35,030 PART OF THE PROJECT THE 1110 00:51:35,030 --> 00:51:38,067 DIFFERENT LABORATORIES WERE SENT 1111 00:51:38,067 --> 00:51:41,136 SAMPLES AND SENT 10 CELL LINES 1112 00:51:41,136 --> 00:51:42,605 AND NUCLEIC ACID FROM 10 CELL 1113 00:51:42,605 --> 00:51:46,775 LINES THAT WAS EXTRACTED AT A 1114 00:51:46,775 --> 00:51:47,543 COLLABORATORS LABORATORY AND 1115 00:51:47,543 --> 00:51:50,179 THERE WERE ALSO NUCLEIC ACID 1116 00:51:50,179 --> 00:51:52,214 FROM 29 CLINICAL SAMPLES THAT 1117 00:51:52,214 --> 00:51:54,316 WERE EXTRACTED IN OUR LABORATORY 1118 00:51:54,316 --> 00:51:55,884 AT MOCA. 1119 00:51:55,884 --> 00:52:00,089 FOR THIS PART OF THE PROJECT, 1120 00:52:00,089 --> 00:52:01,991 MOCA PERFORMED WHOLE EXOME 1121 00:52:01,991 --> 00:52:04,793 SEQUENCING INTO THE SCORE 1122 00:52:04,793 --> 00:52:07,396 ACCORDING TO THE CONSORTIUM GOLD 1123 00:52:07,396 --> 00:52:08,764 STANDARD ALGORITHM. 1124 00:52:08,764 --> 00:52:10,666 AND THAT DATA WAS IN TURN 1125 00:52:10,666 --> 00:52:12,201 COMPARED TO THE PANEL TMB 1126 00:52:12,201 --> 00:52:14,270 SCORES. 1127 00:52:14,270 --> 00:52:16,305 ADDITIONALLY WE DID IN THIS 1128 00:52:16,305 --> 00:52:19,408 PHASE OF THE PROJECT WE USED THE 1129 00:52:19,408 --> 00:52:22,778 TCGA DATA TO GENERATE A 1130 00:52:22,778 --> 00:52:23,746 CALIBRATOR, IF YOU WILL. 1131 00:52:23,746 --> 00:52:25,581 AND WE WERE HOPING THAT 1132 00:52:25,581 --> 00:52:30,119 CALIBRATOR MIGHT HELP US 1133 00:52:30,119 --> 00:52:32,521 HARMONIZE AND ALIGN THE TMB 1134 00:52:32,521 --> 00:52:33,322 SCORES FROM DIFFERENT LABS AND 1135 00:52:33,322 --> 00:52:34,757 YOU'LL SEE IN A MOMENT HOW WE 1136 00:52:34,757 --> 00:52:39,628 DID THAT. 1137 00:52:39,628 --> 00:52:41,597 SO WHAT DID WE SEE? 1138 00:52:41,597 --> 00:52:45,134 TURNS OUT THERE WERE 25 OF 29 1139 00:52:45,134 --> 00:52:51,507 CLINICAL SAMPLES OF TMB, 40 OR 1140 00:52:51,507 --> 00:52:57,279 LESS AROUND WE SAW BIAS ON THE 1141 00:52:57,279 --> 00:52:58,580 IN SILICO ANALYSIS AND THERE 1142 00:52:58,580 --> 00:53:06,755 WERE NOTABLE EXCEPTIONS HERE. 1143 00:53:06,755 --> 00:53:09,124 AND SO WHY MIGHT THAT HAVE BEEN? 1144 00:53:09,124 --> 00:53:10,759 WE'RE IN THE CLINICAL PHASE. 1145 00:53:10,759 --> 00:53:13,395 WE STARTED LOOKING MORE CLOSELY 1146 00:53:13,395 --> 00:53:15,764 AT THIS AND FIRST THING WE DID 1147 00:53:15,764 --> 00:53:24,139 WAS WE ASKED THE LABS TO FILTER 1148 00:53:24,139 --> 00:53:24,773 PATHOGENIC VARIANTS. 1149 00:53:24,773 --> 00:53:26,308 WHY MIGHT WE WANT TO DO THAT? 1150 00:53:26,308 --> 00:53:27,643 THESE PANELS ARE BIASSED. 1151 00:53:27,643 --> 00:53:31,880 IF YOU THINK ABOUT IT THEY'RE 1152 00:53:31,880 --> 00:53:33,982 ALL INTERROGATING CANCER-RELATED 1153 00:53:33,982 --> 00:53:34,783 GENES. 1154 00:53:34,783 --> 00:53:37,753 SO THEY MAY BE BIASSED TOWARDS 1155 00:53:37,753 --> 00:53:39,655 OVER ESTIMATE BEING TMB FOR THAT 1156 00:53:39,655 --> 00:53:39,922 REASON. 1157 00:53:39,922 --> 00:53:42,424 WHAT IF WE ASKED THE LABS TO 1158 00:53:42,424 --> 00:53:46,195 REMOVE KNOWN PATHOGENIC VARIANTS 1159 00:53:46,195 --> 00:53:50,265 WE FIND IN THE COSMIC DATABASE. 1160 00:53:50,265 --> 00:53:53,302 YOU CAN SEE IN THE BOX AND PLOTS 1161 00:53:53,302 --> 00:53:56,739 THE MEDIAN LINE IN THE BOX IS 1162 00:53:56,739 --> 00:53:57,673 MOVING DOWN TOWARDS WHERE THE 1163 00:53:57,673 --> 00:54:00,242 WEST MEDIAN WAS. 1164 00:54:00,242 --> 00:54:04,613 WHEN WE REMOVED THE PATHOGENIC 1165 00:54:04,613 --> 00:54:07,716 VARIANT AND THAT SEEMED TO HELP 1166 00:54:07,716 --> 00:54:10,753 IMPROVE PANEL TMD ESTIMATES. 1167 00:54:10,753 --> 00:54:13,288 MANY LABS INCLUDE SYNONYMOUS 1168 00:54:13,288 --> 00:54:14,757 VARIANTS IN THEIR ESTIMATES AND 1169 00:54:14,757 --> 00:54:16,058 THOUGHT REMOVING THAT WOULD 1170 00:54:16,058 --> 00:54:16,592 ADDITIONALLY HELP. 1171 00:54:16,592 --> 00:54:21,597 THAT SEEMED TO HAVE MINIMAL ON 1172 00:54:21,597 --> 00:54:28,370 PANEL TMB BUT IT DID NARROW THE 1173 00:54:28,370 --> 00:54:31,640 RANGE OF THE BOX SOMEWHAT. 1174 00:54:31,640 --> 00:54:34,343 ANOTHER FACTOR THAT COULD HAVE 1175 00:54:34,343 --> 00:54:36,111 EFFECTED TMB CLOTH IN SOME CASES 1176 00:54:36,111 --> 00:54:44,753 PERHAPS GREATLY IMPACTED IT AND 1177 00:54:44,753 --> 00:54:48,457 WE'LL TALK ABOUT THAT AND 1178 00:54:48,457 --> 00:54:53,028 REMEMBER I SAID THE WHOLE EXOME 1179 00:54:53,028 --> 00:54:54,763 SEQUENCING ASSAY DEFINITIVELY 1180 00:54:54,763 --> 00:54:57,132 IDENTIFIED THE VARIANTS AND 1181 00:54:57,132 --> 00:55:00,135 FILTERED THEM OUT. 1182 00:55:00,135 --> 00:55:02,805 IN THE CLINICAL PHASE WE HAVE 1183 00:55:02,805 --> 00:55:04,773 LABORATORIES AND 14 OF THE 16 1184 00:55:04,773 --> 00:55:06,408 LABS ONLY DO TUMOR SEQUENCING. 1185 00:55:06,408 --> 00:55:09,178 THEY DO NOT SEQUENCE A MATCH 1186 00:55:09,178 --> 00:55:09,745 GERM LINE. 1187 00:55:09,745 --> 00:55:12,214 HOW DO THEY FILTER GERM LINE 1188 00:55:12,214 --> 00:55:13,715 VARIANTS? 1189 00:55:13,715 --> 00:55:17,586 THEY COULD GO TO POPULATION 1190 00:55:17,586 --> 00:55:19,688 DATABASES WHERE THERE'S TENS OF 1191 00:55:19,688 --> 00:55:22,958 THOUSANDS OF NORMAL GERM LINE 1192 00:55:22,958 --> 00:55:31,433 SEQUENCES. 1193 00:55:31,433 --> 00:55:37,005 AND THE OME WAY TO DO THIS IS TO 1194 00:55:37,005 --> 00:55:39,208 FILTER EVERY GERM LINE VARIANT 1195 00:55:39,208 --> 00:55:42,778 YOU SEE IN THE DATABASES. 1196 00:55:42,778 --> 00:55:46,415 THAT'S THE ORANGE 0% DB. 1197 00:55:46,415 --> 00:55:50,185 EVERY VARIANT IS FILTERED AND 1198 00:55:50,185 --> 00:55:53,956 THE WHOLE EXOME IS THE SOLID 1199 00:55:53,956 --> 00:55:54,323 BLACK LINE. 1200 00:55:54,323 --> 00:55:58,427 THE ORANGE IS STARTING TO 1201 00:55:58,427 --> 00:56:00,128 APPROACH THE BLACK BUT EVEN THEN 1202 00:56:00,128 --> 00:56:02,364 IT'S IMPERFECT. 1203 00:56:02,364 --> 00:56:06,101 MOREOVER I WOULD SAY THAT FOR 1204 00:56:06,101 --> 00:56:10,672 THOSE INDIVIDUALS WITH AFRICAN 1205 00:56:10,672 --> 00:56:11,807 ANCESTRY WHERE THERE'S TYPICALLY 1206 00:56:11,807 --> 00:56:13,542 HIGH GENETIC VARIABILITY IT'S 1207 00:56:13,542 --> 00:56:15,143 REALLY IMPORTANT TO DO THIS KIND 1208 00:56:15,143 --> 00:56:18,514 OF FILTERING OR YOUR CALCUL 1209 00:56:18,514 --> 00:56:21,483 CALCULATIONS COULD BE WIDELY 1210 00:56:21,483 --> 00:56:22,050 OFF. 1211 00:56:22,050 --> 00:56:23,452 I TALKED ABOUT ONE OF THE GOALS 1212 00:56:23,452 --> 00:56:29,157 OF THE LAST PART OF THIS PROJECT 1213 00:56:29,157 --> 00:56:35,931 WAS TO GENERATE A CALIBRATION 1214 00:56:35,931 --> 00:56:38,767 APPROACH TO A WHOLE EXOME 1215 00:56:38,767 --> 00:56:39,401 SEQUENCING EQUIVALENT. 1216 00:56:39,401 --> 00:56:42,771 THIS IS WHAT WE DID. 1217 00:56:42,771 --> 00:56:44,706 IT'S ACTUALLY QUITE SIMPLE. 1218 00:56:44,706 --> 00:56:46,775 THE CALIBRATION APPROACH WE USED 1219 00:56:46,775 --> 00:56:52,714 WAS LARGELY BASED ON THE TCGA 1220 00:56:52,714 --> 00:56:52,915 DATA. 1221 00:56:52,915 --> 00:56:54,550 WE SAID EACH LAB LOOKED -- TAKE 1222 00:56:54,550 --> 00:56:57,352 YOUR TCGA DATA AND COMPARE IT TO 1223 00:56:57,352 --> 00:57:00,989 THE WEST TCGA DATA AND FIT A 1224 00:57:00,989 --> 00:57:01,390 REGRESSION LINE. 1225 00:57:01,390 --> 00:57:04,226 THAT'S WHAT THIS LINE IS HERE. 1226 00:57:04,226 --> 00:57:06,094 THAT IS YOUR CALIBRATION LINE 1227 00:57:06,094 --> 00:57:10,766 AND THEN ALL YOU NEED TO DO 1228 00:57:10,766 --> 00:57:15,003 REALLY IS FOR ANY OBSERVED Y0 1229 00:57:15,003 --> 00:57:16,138 VALUE IN THE PANEL YOU BENCHMARK 1230 00:57:16,138 --> 00:57:20,943 IT TO THE REGRESSION LINE, THE 1231 00:57:20,943 --> 00:57:25,180 CALIBRATION LINE AND BETWEEN 1232 00:57:25,180 --> 00:57:29,918 RATE AN EQUIVALENT X0. 1233 00:57:29,918 --> 00:57:33,722 SO THIS IS ROUGHLY 15 MUTATIONS 1234 00:57:33,722 --> 00:57:37,859 PER MEGABASE AND IF YOU 1235 00:57:37,859 --> 00:57:39,895 BENCHMARK AND OFFER THE 1236 00:57:39,895 --> 00:57:41,663 CALIBRATION LINE IT TRANSLATES 1237 00:57:41,663 --> 00:57:44,533 TO 12 MUTATIONS PER MEGABASE AND 1238 00:57:44,533 --> 00:57:46,234 THERE'S A PREDICTION AT 95% 1239 00:57:46,234 --> 00:57:48,203 PREDICTION INTERVAL ON THE HIGH 1240 00:57:48,203 --> 00:57:53,775 END 20 AND LOW END 8. 1241 00:57:53,775 --> 00:57:55,677 THAT'S HOW IT CAN RECALIBRATE 1242 00:57:55,677 --> 00:57:58,480 THE DATA SO IT'S MORE SIMILAR TO 1243 00:57:58,480 --> 00:58:01,049 THE GOLD STANDARD WHOLE EXOME 1244 00:58:01,049 --> 00:58:03,285 SEQUENCING TMB CALCULATION. 1245 00:58:03,285 --> 00:58:04,920 IN PRACTICE HOW WELL DOES THAT 1246 00:58:04,920 --> 00:58:06,154 ACTUALLY WORK? 1247 00:58:06,154 --> 00:58:08,924 SO WE HAVE THE CLINICAL SAMPLE 1248 00:58:08,924 --> 00:58:12,594 SET WE COULD TRY THIS APPROACH 1249 00:58:12,594 --> 00:58:12,761 ON. 1250 00:58:12,761 --> 00:58:17,232 I KNOW THIS IS A BUSY GRAPH BUT 1251 00:58:17,232 --> 00:58:20,736 WHAT YOU'RE SEEING ARE THREE BOX 1252 00:58:20,736 --> 00:58:23,705 AND WHISKER PLOTS. 1253 00:58:23,705 --> 00:58:25,140 THE BOX AND WHISKER PLOT ON 1254 00:58:25,140 --> 00:58:30,779 THEFT IS UNCAL GRIBRATED SAMPLE 1255 00:58:30,779 --> 00:58:34,783 DATA AND IN THE MIDDLE IS IT 1256 00:58:34,783 --> 00:58:45,327 DATA FROM ALL 16 LABS NOW AND ON 1257 00:58:51,266 --> 00:58:55,437 THE WHITE IS DATA FROM THE 10 1258 00:58:55,437 --> 00:58:56,605 CELL LINES. 1259 00:58:56,605 --> 00:58:58,306 IT'S HARD TO SEE SO I'VE BLOWN 1260 00:58:58,306 --> 00:59:00,175 UP ONE SAMPLE TO GIVE A SENSE OF 1261 00:59:00,175 --> 00:59:04,713 WHAT WE SAW. 1262 00:59:04,713 --> 00:59:13,522 THE OTHER IS EACH SAMPLE HAS A 1263 00:59:13,522 --> 00:59:16,191 HORIZONTAL BLACK LIPE AND YOU 1264 00:59:16,191 --> 00:59:18,827 WANT EVERYBODY ALIGNED WITH 1265 00:59:18,827 --> 00:59:19,027 THAT. 1266 00:59:19,027 --> 00:59:24,099 I THINK THE GIST IS WHEN WE 1267 00:59:24,099 --> 00:59:27,202 CALIBRATE TO THE TCGA DATA WE 1268 00:59:27,202 --> 00:59:28,470 GET A BETTER APPROXIMATION TO 1269 00:59:28,470 --> 00:59:29,438 THE WEST VALUE. 1270 00:59:29,438 --> 00:59:33,108 YOU CAN SEE THAT HERE IN THE 1271 00:59:33,108 --> 00:59:33,375 SAMPLE. 1272 00:59:33,375 --> 00:59:36,178 THE BOX AND WHISKER WHICH IS 1273 00:59:36,178 --> 00:59:38,780 OVER ESTIMATING TMB WHEN WE 1274 00:59:38,780 --> 00:59:42,184 CALIBRATE TCGA IS MORE ALIGNED 1275 00:59:42,184 --> 00:59:45,020 WITH IT IN THE BOX IN WHISKER. 1276 00:59:45,020 --> 00:59:46,555 INTERESTINGLY WHEN WE CALIBRATE 1277 00:59:46,555 --> 00:59:49,024 IT TO THE 10 CELL LINES IT 1278 00:59:49,024 --> 00:59:51,460 DIDN'T REALLY HELP. 1279 00:59:51,460 --> 00:59:53,028 BOTTOM LINE IS IF ANYTHING IT 1280 00:59:53,028 --> 00:59:55,330 ACTUALLY INTRODUCED MORE 1281 00:59:55,330 --> 00:59:57,265 VARIANTS IN THE DATA SET PERHAPS 1282 00:59:57,265 --> 01:00:01,369 WE ONLY HAD 10 CELL LINES RATHER 1283 01:00:01,369 --> 01:00:04,706 THAN 4,000 SAMPLES DUE TO 1284 01:00:04,706 --> 01:00:06,641 CALIBRATION. 1285 01:00:06,641 --> 01:00:08,543 IN SUMMARY FOR THE PROJECT AS 1286 01:00:08,543 --> 01:00:12,214 YOU SAW THE TMB IS VERY 1287 01:00:12,214 --> 01:00:15,984 SUBSTANTIALLY BETWEEN 1288 01:00:15,984 --> 01:00:17,986 PARTICIPATING LABS. 1289 01:00:17,986 --> 01:00:26,061 VARIABILITY WAS PRETTY SIMILAR 1290 01:00:26,061 --> 01:00:29,965 AND DOESN'T MATTER AND THE DATA 1291 01:00:29,965 --> 01:00:30,766 IS IMPORTANT. 1292 01:00:30,766 --> 01:00:33,602 IT SEEMS FOR TARGETED PANELS 1293 01:00:33,602 --> 01:00:35,403 FILTERING PATHOGENIC VARIANTS 1294 01:00:35,403 --> 01:00:36,938 WILL HELP ADDRESS THE OVER 1295 01:00:36,938 --> 01:00:38,940 ESTIMATION WE SEE IN SOME OF 1296 01:00:38,940 --> 01:00:49,284 THEM AND ALSO FWERM GERM LINE 1297 01:00:49,284 --> 01:00:55,590 FILTERING AND ONLY USING THIS 1298 01:00:55,590 --> 01:00:57,826 AND WE TALKED ABOUT CALIBRATION 1299 01:00:57,826 --> 01:00:59,995 APPROACHES AND I THINK GOING 1300 01:00:59,995 --> 01:01:02,297 FORWARD WHAT WE HAVE SUGGESTED 1301 01:01:02,297 --> 01:01:04,332 IS THAT LABS MIGHT CONSIDER IN 1302 01:01:04,332 --> 01:01:06,735 THEIR VALIDATION USING TCGA DATA 1303 01:01:06,735 --> 01:01:12,207 TO CALIBRATE AND ALIGN THEIR 1304 01:01:12,207 --> 01:01:14,776 PANEL TO THE GOLD STANDARD WEST 1305 01:01:14,776 --> 01:01:18,780 DATA WE SAW. 1306 01:01:18,780 --> 01:01:24,219 SO I'M GOING TO WRAP THIS UP AND 1307 01:01:24,219 --> 01:01:25,153 THIS PART OF THE PRESENTATION UP 1308 01:01:25,153 --> 01:01:26,087 RIGHT NOW. 1309 01:01:26,087 --> 01:01:28,023 I WANT TO ACKNOWLEDGE LISA 1310 01:01:28,023 --> 01:01:33,395 McSHANE WHO AGAIN WHO DID THE 1311 01:01:33,395 --> 01:01:36,198 STATISTICS WITH THEIR GROUP. 1312 01:01:36,198 --> 01:01:41,803 WE HAVE AN R PACKAGE THAT ASSAY 1313 01:01:41,803 --> 01:01:46,308 DEVELOPERS CAN USE DEVELOPED IN 1314 01:01:46,308 --> 01:01:47,042 LISA'S LABORATORY AND THAT 1315 01:01:47,042 --> 01:01:51,746 CALIBRATION PACKAGE WILL DO THE 1316 01:01:51,746 --> 01:01:54,216 CALIBRATION I TALKED ABOUT. 1317 01:01:54,216 --> 01:01:56,852 THERE ARE INDIVIDUALS FROM OUR 1318 01:01:56,852 --> 01:02:03,325 TEAM WHO CONTRIBUTED AS WELL AND 1319 01:02:03,325 --> 01:02:06,194 FRIENDS OF CANCER RESEARCH AND A 1320 01:02:06,194 --> 01:02:08,930 LARGE CONSORTIUM OF PARTICIPANTS 1321 01:02:08,930 --> 01:02:12,100 WHICH I'M SHOWING HERE. 1322 01:02:12,100 --> 01:02:14,769 NEXT TIME I WANT TO TALK ABOUT A 1323 01:02:14,769 --> 01:02:15,904 MORE RECENT PROJECT THAT WE'VE 1324 01:02:15,904 --> 01:02:17,906 BEEN WORKING ON WITH FRIENDS OF 1325 01:02:17,906 --> 01:02:19,407 CANCER RESEARCH AND WE'VE 1326 01:02:19,407 --> 01:02:21,509 SUBMITTED A MANUSCRIPT TO THE 1327 01:02:21,509 --> 01:02:24,346 JOURNAL OF CLINICAL ONCOLOGY AND 1328 01:02:24,346 --> 01:02:25,914 I'M GOING TO SHOW SOME OF THOSE 1329 01:02:25,914 --> 01:02:27,482 FINDINGS IN A MOMENT. 1330 01:02:27,482 --> 01:02:37,959 IT'S AN EFFORT TO HARMONIZE 1331 01:02:38,927 --> 01:02:39,394 HOMOLOGOUS RECOMBINATION 1332 01:02:39,394 --> 01:02:40,695 DEFICIENCY AND HOMOLOGOUS 1333 01:02:40,695 --> 01:02:42,197 RECOMBINATION DEFICIENCY 1334 01:02:42,197 --> 01:02:45,033 MEASURES DEFECTS IN DNA REPAIR. 1335 01:02:45,033 --> 01:02:48,637 SPECIFICALLY THIS IS EFFECTS IN 1336 01:02:48,637 --> 01:02:51,673 DOUBLE-STRANDED DNA BREAK 1337 01:02:51,673 --> 01:02:52,274 REPAIR. 1338 01:02:52,274 --> 01:02:55,076 THE HALLMARK OF HRD WOULD BE 1339 01:02:55,076 --> 01:02:57,612 MUTATIONS AND BRCA 1 AND 2 1340 01:02:57,612 --> 01:02:57,812 GENES. 1341 01:02:57,812 --> 01:03:03,919 YOU CAN GENERALLY THINK OF HRD 1342 01:03:03,919 --> 01:03:05,420 IN TWO CATEGORIES. 1343 01:03:05,420 --> 01:03:08,690 THERE'S CAUSES THAT WOULD BE 1344 01:03:08,690 --> 01:03:11,693 MUTATIONS IN THE BRCA 1 AND 2 1345 01:03:11,693 --> 01:03:16,364 GENES AND OTHER PATHWAY GENES 1346 01:03:16,364 --> 01:03:18,199 LIKE POLL B2 FOR EXAMPLE AND 1347 01:03:18,199 --> 01:03:21,236 THERE'S EXAMPLES AND 1348 01:03:21,236 --> 01:03:21,569 CONSEQUENCES. 1349 01:03:21,569 --> 01:03:24,205 THE CONSEQUENCES OF DEFECTS IN 1350 01:03:24,205 --> 01:03:25,040 THE HOMOLOGOUS RECOMBINATION 1351 01:03:25,040 --> 01:03:28,576 DEFICIENCY IS YOU INTRODUCE 1352 01:03:28,576 --> 01:03:30,178 GENOMIC SCARS. 1353 01:03:30,178 --> 01:03:36,217 LOSS OF HETRO ZYGOSITY AND SOME 1354 01:03:36,217 --> 01:03:38,787 LABS MEASURE THOSE IN ADDITION 1355 01:03:38,787 --> 01:03:46,594 TO MEASURES DEFECTS IN 1356 01:03:46,594 --> 01:03:48,029 HOMOLOGOUS RECOMBINATION REPAIR 1357 01:03:48,029 --> 01:03:48,229 GENES. 1358 01:03:48,229 --> 01:03:54,202 IT'S TURNED OUT TO BE AN 1359 01:03:54,202 --> 01:03:56,271 IMPORTANT BIOMARKER. 1360 01:03:56,271 --> 01:03:57,172 THE CHALLENGE IS THERE'S 1361 01:03:57,172 --> 01:03:59,240 DIFFERENT WAYS TO APPRECIATE AND 1362 01:03:59,240 --> 01:04:00,642 TO MEASURE HRD. 1363 01:04:00,642 --> 01:04:08,483 IT'S UNCLEAR HOW WE ALL ALIGN. 1364 01:04:08,483 --> 01:04:10,552 AND IT'S IMPORTANT TO BRING A 1365 01:04:10,552 --> 01:04:11,753 PUBLIC-PRIVATE CONSORTIUM 1366 01:04:11,753 --> 01:04:15,957 TOGETHER AND FRY TO ADDRESS IT 1367 01:04:15,957 --> 01:04:16,624 HOW THEY DIFFERENT AND HOW WE 1368 01:04:16,624 --> 01:04:26,935 MIGHT ALIGN THEM. 1369 01:04:29,904 --> 01:04:33,441 OUR LAB PARTICIPATED AND LISA'S 1370 01:04:33,441 --> 01:04:36,711 GROUP PARTICIPATE AND WE HAD 1371 01:04:36,711 --> 01:04:40,382 FOLKS FROM FDA ON BI-WEEKLY 1372 01:04:40,382 --> 01:04:41,850 CALLS AND HAD KEY STAKEHOLDERS 1373 01:04:41,850 --> 01:04:42,283 FROM INDUSTRY. 1374 01:04:42,283 --> 01:04:45,120 I'M GOING TO FOCUS ON WHAT WE'RE 1375 01:04:45,120 --> 01:04:47,756 CALLING PHASE 2 OF THE PROJECT 1376 01:04:47,756 --> 01:04:49,057 TODAY WITH YOU. 1377 01:04:49,057 --> 01:04:54,229 LIKE WITH THE TMB PROJECT IN THE 1378 01:04:54,229 --> 01:04:58,800 IN SILICO ANALYSIS ON TCGA DATA 1379 01:04:58,800 --> 01:05:05,573 AND CLINICAL ANALYSIS. 1380 01:05:05,573 --> 01:05:12,213 SO LET'S FIRST TALK ABOUT THE 1381 01:05:12,213 --> 01:05:18,219 IN SILICO ANALYSIS ON PATIENTS 1382 01:05:18,219 --> 01:05:20,088 AND AS EVERYBODY APPRECIATES 1383 01:05:20,088 --> 01:05:26,528 THERE'S NO CANCER TIED TO THE 1384 01:05:26,528 --> 01:05:33,768 HIGHER PREVALENCE OF HRD AND 1385 01:05:33,768 --> 01:05:35,136 IT'S PROOF OF CONCEPT STUDIO AND 1386 01:05:35,136 --> 01:05:41,509 HAD ACCESS TO THE TCGA DATA AND 1387 01:05:41,509 --> 01:05:44,412 SENT THE RAW DATA FILES AND BRCA 1388 01:05:44,412 --> 01:05:47,415 GERM LINE MUTATION FILES TO 11 1389 01:05:47,415 --> 01:05:47,749 PARTICIPANTS. 1390 01:05:47,749 --> 01:05:51,019 THEY RAN THE DATA FILES THROUGH 1391 01:05:51,019 --> 01:05:59,027 THEIR HRD PIPELINE AND NCI AND 1392 01:05:59,027 --> 01:06:02,597 THE ENTIRE GROUP REVIEWED THE 1393 01:06:02,597 --> 01:06:03,364 FINDINGS. 1394 01:06:03,364 --> 01:06:06,167 HERE'S THE SUMMARY OF THE IN 1395 01:06:06,167 --> 01:06:06,534 SILICO RESULTS. 1396 01:06:06,534 --> 01:06:11,005 ON THE LEFT WE'RE LOOKING AT THE 1397 01:06:11,005 --> 01:06:13,842 PERCENT HRD AS CALLED BY THE 11 1398 01:06:13,842 --> 01:06:15,710 DIFFERENT IF ASSAY DEVELOPERS. 1399 01:06:15,710 --> 01:06:20,115 THE MEDIAN WAS 49%. 1400 01:06:20,115 --> 01:06:24,252 49% WERE HRD POSITIVE CASES 1401 01:06:24,252 --> 01:06:26,754 AMONG 348 ANALYZED. 1402 01:06:26,754 --> 01:06:29,424 YOU CAN SEE THE PERCENT HRD 1403 01:06:29,424 --> 01:06:31,860 POSITIVE CASES RANGED WIDELY 1404 01:06:31,860 --> 01:06:37,065 FROM A LOW OF 9% TO A HIGH OF 1405 01:06:37,065 --> 01:06:37,298 67%. 1406 01:06:37,298 --> 01:06:39,601 CERTAINLY HIGHER THAN I WAS 1407 01:06:39,601 --> 01:06:39,868 EXPECTING. 1408 01:06:39,868 --> 01:06:44,572 IF WE DRILL DOWN DEEPER INTO THE 1409 01:06:44,572 --> 01:06:46,407 DATA YOU CAN SEE OVER HERE ON 1410 01:06:46,407 --> 01:06:50,945 THE HEAT MAP ON THE RIGHT EACH 1411 01:06:50,945 --> 01:06:52,147 ROW IS ASSAY. 1412 01:06:52,147 --> 01:06:55,150 EACH COLUMN IS A DIFFERENT 1413 01:06:55,150 --> 01:06:58,019 SAMPLE AND YOU CAN SEE ALSO THE 1414 01:06:58,019 --> 01:07:00,722 DIFFERENT APPROACHES THE LABS 1415 01:07:00,722 --> 01:07:03,725 ARE USING TO CALL HRD. 1416 01:07:03,725 --> 01:07:08,429 ALL LABS INTERROGATE BRCA 1 AND 1417 01:07:08,429 --> 01:07:13,067 2 AND THEY'RE INTERROGATING 1418 01:07:13,067 --> 01:07:17,672 GENOMIC LOSS OF HETEROZYGOSITY 1419 01:07:17,672 --> 01:07:21,342 AND ALL MEASURES OF GENOMIC 1420 01:07:21,342 --> 01:07:21,609 SCARRING. 1421 01:07:21,609 --> 01:07:23,878 WE HAVE A NUMBER OF LABS 1422 01:07:23,878 --> 01:07:25,547 INTERROGATING ONE OR MORE AND WE 1423 01:07:25,547 --> 01:07:32,187 HAVE A NUMBER OF LABS THAT LOOK 1424 01:07:32,187 --> 01:07:32,787 AT HOMOLOGOUS RECOMBINATION 1425 01:07:32,787 --> 01:07:33,821 GENES AND REPORT OUT BASED ON 1426 01:07:33,821 --> 01:07:39,227 WHETHER THEY SEE MUTATION IN ONE 1427 01:07:39,227 --> 01:07:45,633 OF THOSE GENES THEN WE HAVE THE 1428 01:07:45,633 --> 01:07:47,268 BRCA MUTATIONS IDENTIFIED BY THE 1429 01:07:47,268 --> 01:07:48,236 LABS. 1430 01:07:48,236 --> 01:07:52,674 IT'S COMFORTING TO SEE HERE THAT 1431 01:07:52,674 --> 01:07:54,909 ALMOST EVERY LAB, NOT EVERY LAB 1432 01:07:54,909 --> 01:07:56,844 INTERESTINGLY ENOUGH BUT ALMOST 1433 01:07:56,844 --> 01:07:59,147 EVERY LAB WAS PRETTY MUCH IN 1434 01:07:59,147 --> 01:08:01,983 AGREEMENT ON WHAT WAS A 1435 01:08:01,983 --> 01:08:04,252 DELETERIOUS BRCA MUTATION. 1436 01:08:04,252 --> 01:08:06,254 SO I'M GOING TO MOVE ON NOW TO 1437 01:08:06,254 --> 01:08:08,556 THE CLINICAL PART OF THE STUDY. 1438 01:08:08,556 --> 01:08:12,026 IN THIS PART OF THE STUDY WE 1439 01:08:12,026 --> 01:08:14,629 SOURCED 90 ARCHIVAL VARIANT 1440 01:08:14,629 --> 01:08:17,665 CANCER SAMPLES FROM THE LAB OF 1441 01:08:17,665 --> 01:08:19,467 THE UNIVERSITY OF ALABAMA 1442 01:08:19,467 --> 01:08:20,168 BIRMINGHAM. 1443 01:08:20,168 --> 01:08:22,704 THE SPECIMENS WERE SENT TO OUR 1444 01:08:22,704 --> 01:08:25,573 LAB AT MOCA. 1445 01:08:25,573 --> 01:08:27,875 WE DID THE EXTRACTION AND 1446 01:08:27,875 --> 01:08:29,877 ALLOCATED THE SAMPLES AND SENT 1447 01:08:29,877 --> 01:08:31,946 THEM OUT TO 17 PARTICIPATING 1448 01:08:31,946 --> 01:08:32,247 LABS. 1449 01:08:32,247 --> 01:08:36,251 WE HAD 17 LABS PARTICIPATING IN 1450 01:08:36,251 --> 01:08:41,089 THE CLINICAL ANALYSIS PHASE. 1451 01:08:41,089 --> 01:08:43,491 THEY REPORTED THEIR HRD SCORES 1452 01:08:43,491 --> 01:08:47,295 BACK TO LISA AND HER TEAM AT THE 1453 01:08:47,295 --> 01:08:50,598 NCI AROUND THEN THE ENTIRE GROUP 1454 01:08:50,598 --> 01:08:56,004 REVIEWED THE FINDINGS AND I WANT 1455 01:08:56,004 --> 01:09:06,547 TO CALL OUT WE DON'T HAVE AGOLD 1456 01:09:06,814 --> 01:09:07,882 STANDARD FOR HRD. 1457 01:09:07,882 --> 01:09:08,750 THERE'S NOT ONE I THINK IT'S 1458 01:09:08,750 --> 01:09:09,784 FAIR TO SAY. 1459 01:09:09,784 --> 01:09:12,287 MORE ABOUT THE SAMPLE 1460 01:09:12,287 --> 01:09:14,055 CHARACTERISTICS. 1461 01:09:14,055 --> 01:09:15,523 THESE SAMPLES ALL CAME FROM 1462 01:09:15,523 --> 01:09:19,727 SURGERIES AND REPRESENTED STAGE 1463 01:09:19,727 --> 01:09:21,996 3 OR 4 VARIANTS OF CANCER. 1464 01:09:21,996 --> 01:09:25,933 IN TERMS OF THE ASSAYS, I 1465 01:09:25,933 --> 01:09:28,036 MENTIONED THERE WERE 17 1466 01:09:28,036 --> 01:09:28,369 PARTICIPANTS. 1467 01:09:28,369 --> 01:09:30,238 THEY ALL HAD BRCA 1 AND 2 1468 01:09:30,238 --> 01:09:30,605 MUTATIONS. 1469 01:09:30,605 --> 01:09:32,340 IN ADDITION YOU CAN SEE IN TERMS 1470 01:09:32,340 --> 01:09:37,545 OF GENOMIC SCARRING, THE MOST 1471 01:09:37,545 --> 01:09:44,285 COMMONLY INTERROGATED SCAR WAS 1472 01:09:44,285 --> 01:09:46,254 GENOMIC EOH AND WE HAD ALMOST 1473 01:09:46,254 --> 01:09:48,890 60% OF LABS LOOK AT MUTATIONS 1474 01:09:48,890 --> 01:09:54,495 BEYOND BRCA 1 AND BRCA 2 AND HRD 1475 01:09:54,495 --> 01:09:57,332 BASED ON WHETHER THEY SAW 1476 01:09:57,332 --> 01:10:02,136 MUTATION IN ANY OF THOSE GENES. 1477 01:10:02,136 --> 01:10:04,839 IN TERMS OF THE CLINICAL PHASE 1478 01:10:04,839 --> 01:10:08,042 IS SIMILAR TO THE IN SILICO 1479 01:10:08,042 --> 01:10:11,412 PHASE MEAN AND MEDIAN WERE 82% 1480 01:10:11,412 --> 01:10:12,513 POSITIVITY WITH THE 17 1481 01:10:12,513 --> 01:10:13,581 PARTICIPANTS. 1482 01:10:13,581 --> 01:10:16,217 AGAIN, A VERY BROAD RANGE FROM A 1483 01:10:16,217 --> 01:10:19,454 LOW END OF 23% TO A HIGH END OF 1484 01:10:19,454 --> 01:10:26,761 74%. 1485 01:10:26,761 --> 01:10:33,968 I MENTIONED THERE WAS NO GOLD 1486 01:10:33,968 --> 01:10:34,769 STANDARD AND STARTED COMPARING 1487 01:10:34,769 --> 01:10:37,105 LABS TO ONE ANOTHER AND MANY ARE 1488 01:10:37,105 --> 01:10:38,773 FAMILIAR WITH THE AGREEMENT AND 1489 01:10:38,773 --> 01:10:42,176 DOING PAIR WISE COMPARISONS 1490 01:10:42,176 --> 01:10:45,713 BETWEEN ASSAYS THERE IS NO GOLD 1491 01:10:45,713 --> 01:10:45,980 STANDARD. 1492 01:10:45,980 --> 01:10:48,249 THAT IS SIMPLY THE PERCENTAGE OF 1493 01:10:48,249 --> 01:10:51,452 SAMPLES THAT TEST POSITIVE BY 1494 01:10:51,452 --> 01:10:56,257 ONE TEST SAY, ASSAY A FOUND TO 1495 01:10:56,257 --> 01:10:58,760 BE POSITIVE BY ASSAY B. 1496 01:10:58,760 --> 01:11:01,429 AN EXAMPLE TABLE SO FOR EXAMPLE 1497 01:11:01,429 --> 01:11:05,833 IF WE WERE COMPARING ASSAY A TO 1498 01:11:05,833 --> 01:11:09,337 B, ASSAY A SEES POSITIVE CASES 1499 01:11:09,337 --> 01:11:12,240 AND AMONG THEM ASSAY B SAW TWO 1500 01:11:12,240 --> 01:11:13,975 OF THEM. 1501 01:11:13,975 --> 01:11:17,345 THE POSITIVE PERCENT AGREEMENT 1502 01:11:17,345 --> 01:11:18,646 WOULD BE 50%. 1503 01:11:18,646 --> 01:11:22,917 WE ALSO FLIPPED THE COMPARISON 1504 01:11:22,917 --> 01:11:25,086 AND MADE B THE REFERENCE AND A 1505 01:11:25,086 --> 01:11:27,989 66% BPA. 1506 01:11:27,989 --> 01:11:29,857 WE HAD 17 ASSAYS AND IF YOU DO 1507 01:11:29,857 --> 01:11:33,728 THE CALCULATION IT TURNS OUT TO 1508 01:11:33,728 --> 01:11:35,329 BE 136 POSSIBLE PAIRS. 1509 01:11:35,329 --> 01:11:38,766 EACH IN TWO DIRECTIONS. 1510 01:11:38,766 --> 01:11:41,302 SO WE GOT 272 PAIR WISE 1511 01:11:41,302 --> 01:11:42,970 COMPARISONS WE'RE DOING AND ALL 1512 01:11:42,970 --> 01:11:48,242 THAT DATA IS SUMMARIZED HERE. 1513 01:11:48,242 --> 01:11:50,478 LOOKING AT ALL SAMPLES FIRST. 1514 01:11:50,478 --> 01:11:58,486 OVER ON THE LEFT YOU SEE THE 1515 01:11:58,486 --> 01:11:59,887 MEDIAN POSITIVE PAIR WISE 1516 01:11:59,887 --> 01:12:02,523 AGREEMENT AND POSITIVE PERCENT 1517 01:12:02,523 --> 01:12:06,427 AGREEMENT, EXCUSE ME, IS 83% AND 1518 01:12:06,427 --> 01:12:11,699 ON THE AGREEMENT REALLY VARIED 1519 01:12:11,699 --> 01:12:13,234 QUITE DRAMATICALLY DEPENDING ON 1520 01:12:13,234 --> 01:12:17,405 THE PAIR OF ASSAYS THAT WERE 1521 01:12:17,405 --> 01:12:17,939 PREPA 1522 01:12:17,939 --> 01:12:18,206 PREPARED. 1523 01:12:18,206 --> 01:12:19,273 THAT'S POSITIVE PERCENT 1524 01:12:19,273 --> 01:12:19,540 AGREEMENT. 1525 01:12:19,540 --> 01:12:22,610 WE ALSO LOOKED AT NEGATIVE 1526 01:12:22,610 --> 01:12:24,745 PERCENT AGREEMENT USING THE SAME 1527 01:12:24,745 --> 01:12:27,215 APPROACH THAT I DESCRIBED FOR 1528 01:12:27,215 --> 01:12:28,382 POSITIVE PERCENT AGREEMENT. 1529 01:12:28,382 --> 01:12:31,285 AND THEN WE LOOKED SPECIFICALLY 1530 01:12:31,285 --> 01:12:33,721 AT BRCA 1 AND BRCA 2 MUTATIONS 1531 01:12:33,721 --> 01:12:36,424 AND THERE WERE 23 CASES WHERE AT 1532 01:12:36,424 --> 01:12:40,928 LEAST ONE LAB FOUND A BRCA 1 OR 1533 01:12:40,928 --> 01:12:43,798 BRCA 2 MUTATION AND I THINK 1534 01:12:43,798 --> 01:12:47,101 SOMEWHAT REASSURINGLY THE MEDIAN 1535 01:12:47,101 --> 01:12:50,771 WAS 100% SPECIFICALLY FOR BRCA 1 1536 01:12:50,771 --> 01:12:56,210 AND 2. 1537 01:12:56,210 --> 01:13:02,550 NOW, IF YOU TAKE THE OTHER CASES 1538 01:13:02,550 --> 01:13:06,320 THE POSITIVE FELL FROM 83% TO 1539 01:13:06,320 --> 01:13:14,929 67%. 1540 01:13:14,929 --> 01:13:16,664 THESE ARE ASSAYS USING IS 1541 01:13:16,664 --> 01:13:18,332 SCARRING APPROACHES AND IT'S 1542 01:13:18,332 --> 01:13:21,369 TELLING US THERE'S NOT AS GOOD 1543 01:13:21,369 --> 01:13:23,471 AGREEMENT WITH SCARRING AS WITH 1544 01:13:23,471 --> 01:13:27,308 THE BRA CA APPROACHES AND -- 1545 01:13:27,308 --> 01:13:33,247 BRCA APPROACHES AND THAT'S TO BE 1546 01:13:33,247 --> 01:13:33,514 EXPECTED. 1547 01:13:33,514 --> 01:13:36,417 WHAT IS ASSOCIATED BETWEEN 1548 01:13:36,417 --> 01:13:38,352 AGREEMENTS WITH THE LAB. 1549 01:13:38,352 --> 01:13:40,488 THIS HEAT MAP LOOKS AT SOME OF 1550 01:13:40,488 --> 01:13:41,756 THOSE AND I'LL CALL THEM OUT 1551 01:13:41,756 --> 01:13:43,391 RIGHT NOW. 1552 01:13:43,391 --> 01:13:50,197 STARTING WITH BRCA 1 AND 2, IT'S 1553 01:13:50,197 --> 01:13:51,933 COMFORTING TO KNOW ALL THE LABS 1554 01:13:51,933 --> 01:13:54,168 ARE DOING A GOOD JOB OF CALLING 1555 01:13:54,168 --> 01:13:56,103 THOSE MUTATIONS, AS I SAID. 1556 01:13:56,103 --> 01:13:57,004 THEN THERE'S RACE. 1557 01:13:57,004 --> 01:14:02,343 I DISAPPOINT KNOW -- DON'T KNOW 1558 01:14:02,343 --> 01:14:03,811 WE EXPECTED RACE TO FIND AN 1559 01:14:03,811 --> 01:14:06,247 INFLUENCE ON THE LAB TO CALL HRD 1560 01:14:06,247 --> 01:14:11,419 AND IT DIDN'T. 1561 01:14:11,419 --> 01:14:12,653 CCNE1 AMPLIFICATION. 1562 01:14:12,653 --> 01:14:16,123 THERE'S A BODY OF LITERATURE 1563 01:14:16,123 --> 01:14:18,793 EXCLUSIVE WITH HRD POSITIVITY 1564 01:14:18,793 --> 01:14:19,760 AND SEEN IN THE COHORT AS WELL 1565 01:14:19,760 --> 01:14:22,563 AND A COUPLE MORE THINGS I WANT 1566 01:14:22,563 --> 01:14:23,297 TO POINT OUT. 1567 01:14:23,297 --> 01:14:25,600 ASSAY USE. 1568 01:14:25,600 --> 01:14:28,903 WE HAD A MIXTURE OF PARTICIPANTS 1569 01:14:28,903 --> 01:14:32,807 WITH CLINICAL ASSAYS AS WELL AS 1570 01:14:32,807 --> 01:14:36,277 WITH RESEARCHER ASSAYS AND THEY 1571 01:14:36,277 --> 01:14:38,746 SEEMED TO DO EQUALLY WELL AND NO 1572 01:14:38,746 --> 01:14:42,249 BIG DIFFERENCE IN COMPARING 1573 01:14:42,249 --> 01:14:46,754 BETWEEN THE TWO BUT INTERESTING 1574 01:14:46,754 --> 01:14:50,057 LY LOOKING AT THE HRD POSITIVE 1575 01:14:50,057 --> 01:14:52,994 CASES THAT DID NOT HAVE BRCA 1576 01:14:52,994 --> 01:14:55,162 MUTATIONS IS THIS CLUSTER ON THE 1577 01:14:55,162 --> 01:14:57,798 LEFT, THERE WAS QUITE A BIT OF 1578 01:14:57,798 --> 01:14:59,200 AGREEMENT EXCEPT HERE NEAR THE 1579 01:14:59,200 --> 01:14:59,367 TOP. 1580 01:14:59,367 --> 01:15:02,570 YOU CAN SEE THERE WERE THREE 1581 01:15:02,570 --> 01:15:04,405 ASSAYS THAT WERE KIND OF 1582 01:15:04,405 --> 01:15:04,672 OUTLIERS. 1583 01:15:04,672 --> 01:15:08,509 NOW, ONE OF THEM, THE TOP ONE, 1584 01:15:08,509 --> 01:15:12,713 USES GENOMIC SCARRING APPROACHES 1585 01:15:12,713 --> 01:15:16,450 TO CALL BRCA MUTATIONS AND 1586 01:15:16,450 --> 01:15:18,285 THEY'RE NOT REALLY AGREEING WITH 1587 01:15:18,285 --> 01:15:28,629 MOST THE OTHER LABS. 1588 01:15:36,337 --> 01:15:43,110 WE LOOKED AT MUTATIONS AND NOT 1589 01:15:43,110 --> 01:15:45,146 GOING TO FIND HRD SAMPLES 1590 01:15:45,146 --> 01:15:46,614 POSITIVE AS OTHER LABS USING 1591 01:15:46,614 --> 01:15:48,282 GENOMIC SCARRING APPROACHES. 1592 01:15:48,282 --> 01:15:49,550 THAT PROBABLY EXPLAINS THE 1593 01:15:49,550 --> 01:15:56,023 DISCORDANTS WE'RE SEEING HERE. 1594 01:15:56,023 --> 01:15:59,393 I WANTED TO MENTION A FEW MORE 1595 01:15:59,393 --> 01:16:00,461 FACTORS WE LOOKED INTO. 1596 01:16:00,461 --> 01:16:04,365 ONE IS THE SAMPLE QUALITY. 1597 01:16:04,365 --> 01:16:06,300 SO TUMOR PURITY YOU MIGHT THINK 1598 01:16:06,300 --> 01:16:08,569 THAT WOULD HAVE AN WHY IMPACT 1599 01:16:08,569 --> 01:16:10,571 AND THERE WERE STUD THAT 1600 01:16:10,571 --> 01:16:12,306 SUGGESTED IT DOES IF YOU START 1601 01:16:12,306 --> 01:16:13,741 TO GET TOO LOW YOU HAVE 1602 01:16:13,741 --> 01:16:17,278 DIFFICULTY IDENTIFYING GENOMIC 1603 01:16:17,278 --> 01:16:22,016 SCARS SAY DOWN AROUND 30%, 40%. 1604 01:16:22,016 --> 01:16:23,084 WE DIDN'T SEE ANY CORRELATION 1605 01:16:23,084 --> 01:16:26,987 WITH TUMOR PURITY AND THAT'S 1606 01:16:26,987 --> 01:16:28,856 PROBABLY BECAUSE WE REQUIRED FOR 1607 01:16:28,856 --> 01:16:31,792 THE STUDY A TUMOR CELLULARITY OF 1608 01:16:31,792 --> 01:16:33,828 AT LEAST 70%. 1609 01:16:33,828 --> 01:16:35,229 WE WANTED TO CONTROL THE 1610 01:16:35,229 --> 01:16:38,766 VARIABLES AND NOT HAVE THEM 1611 01:16:38,766 --> 01:16:42,336 INTERFERE WITH THIS ANALYSIS BUT 1612 01:16:42,336 --> 01:16:45,339 IN FUTURE STUDIES ONE COULD 1613 01:16:45,339 --> 01:16:50,244 INCLUDE SAMPLES WITH NOT ONLY 1614 01:16:50,244 --> 01:16:52,146 POORER DNA PURITY AND QUALITY. 1615 01:16:52,146 --> 01:16:54,215 IN THIS STUDY WE TRIED TO 1616 01:16:54,215 --> 01:16:55,883 CONTROL PRE-ANALYTICAL VARIABLES 1617 01:16:55,883 --> 01:17:01,288 AND INCLUDED SAMPLES THAT WERE 1618 01:17:01,288 --> 01:17:04,992 VERY GOOD QUALITY BELOW THE DNA 1619 01:17:04,992 --> 01:17:06,093 INTEGRITY SCORE OF 2. 1620 01:17:06,093 --> 01:17:07,495 AND THE AGE OF THE BLOCK. 1621 01:17:07,495 --> 01:17:09,063 WE HAD BLOCKS IN THE STUDY THAT 1622 01:17:09,063 --> 01:17:11,065 WERE 10 YEARS OLD OR OLDER AND 1623 01:17:11,065 --> 01:17:12,333 DIDN'T SEEM TO MATTER. 1624 01:17:12,333 --> 01:17:14,769 SO THE AGE OF THE BLOCK WAS NOT 1625 01:17:14,769 --> 01:17:16,837 A FACTOR. 1626 01:17:16,837 --> 01:17:18,072 THERE WAS HOWEVER, SOME 1627 01:17:18,072 --> 01:17:19,874 CORRELATION WITH THE ASSAY 1628 01:17:19,874 --> 01:17:20,875 CUT-OFF LOOKING AT THE ASSAY 1629 01:17:20,875 --> 01:17:22,510 MORE CLOSELY. 1630 01:17:22,510 --> 01:17:25,312 AS YOU MIGHT EXPECT AND AS THESE 1631 01:17:25,312 --> 01:17:27,515 TWO GRAPHS SHOW, AS YOU APPROACH 1632 01:17:27,515 --> 01:17:32,019 THE ASSAY CUT-OFF AND THAT'S THE 1633 01:17:32,019 --> 01:17:35,289 RED LINE HERE YOU CAN SEE THE 1634 01:17:35,289 --> 01:17:37,925 AGREEMENT OF THIS ASSAY WITH 1635 01:17:37,925 --> 01:17:40,961 OTHER ASSAYS GO DOWN AND THAT'S 1636 01:17:40,961 --> 01:17:42,663 REPRESENTED BY THIS BLUE CURVE 1637 01:17:42,663 --> 01:17:45,800 HERE AND THE AGREEMENT IS ON THE 1638 01:17:45,800 --> 01:17:46,467 Y AXIS. 1639 01:17:46,467 --> 01:17:48,335 SO AGAIN, I DON'T KNOW IT'S 1640 01:17:48,335 --> 01:17:48,669 UNEXPECTED. 1641 01:17:48,669 --> 01:17:50,771 I THINK THAT WOULD PROBABLY BE 1642 01:17:50,771 --> 01:17:52,873 TRUE FOR ANY ASSAY WHEN YOU'RE 1643 01:17:52,873 --> 01:18:02,383 LOOKING NEAR THE ASSAY CUT-OFF. 1644 01:18:02,383 --> 01:18:04,084 AND THE LAST THING I WANT TO 1645 01:18:04,084 --> 01:18:07,955 SHOW IS DATA GENERATED LOOKING 1646 01:18:07,955 --> 01:18:10,758 AT CORRELATIONS BETWEEN HRD AND 1647 01:18:10,758 --> 01:18:12,359 CLINICAL OUTCOMES. 1648 01:18:12,359 --> 01:18:13,327 WE'RE VERY FORTUNATE IN THE 1649 01:18:13,327 --> 01:18:15,462 COHORT AND IT WAS ANNOTATED WITH 1650 01:18:15,462 --> 01:18:23,304 CLINICAL OUTCOME AND ALL 1651 01:18:23,304 --> 01:18:24,405 RECEIVED PLATINUM BASED THERAPY 1652 01:18:24,405 --> 01:18:26,607 AND BEFORE I POINT OUT THE 1653 01:18:26,607 --> 01:18:28,709 SURVIVAL CURVES I WANT TO POINT 1654 01:18:28,709 --> 01:18:30,244 OUT THE WAY WE GROUPED THE 1655 01:18:30,244 --> 01:18:33,214 SAMPLES WAS IN TREE CLUSTERS. 1656 01:18:33,214 --> 01:18:36,016 WE HAVE HERE THE NOT-HRD CLUSTER 1657 01:18:36,016 --> 01:18:37,985 BASED ON MAJORITY RULE. 1658 01:18:37,985 --> 01:18:39,920 WHATEVER MOST THE LABS IDENTIFY 1659 01:18:39,920 --> 01:18:42,122 AS NON-HRD WE INCLUDED IN THE 1660 01:18:42,122 --> 01:18:42,389 CLUSTER. 1661 01:18:42,389 --> 01:18:43,757 SIMILARLY YOU HAVE A BRCA 1662 01:18:43,757 --> 01:18:50,731 CLUSTER HERE AND THEN WE HAVE AN 1663 01:18:50,731 --> 01:18:52,299 HRD-POSITIVE CLUSTER NOT BRCA 1664 01:18:52,299 --> 01:18:54,668 AND CALL IT THE SEQUENCES 1665 01:18:54,668 --> 01:18:57,238 CLUSTER BUT THAT'S HRD POSITIVE 1666 01:18:57,238 --> 01:18:59,874 JUST NOT BRCA. 1667 01:18:59,874 --> 01:19:01,775 IF YOU LOOK AT THE OCCURRENCE 1668 01:19:01,775 --> 01:19:04,011 FOR SURVIVAL YOU SEE A TREND 1669 01:19:04,011 --> 01:19:08,616 TOWARDS THE BRCA CLUSTER HAVING 1670 01:19:08,616 --> 01:19:13,287 BETTER SURVIVAL. 1671 01:19:13,287 --> 01:19:14,755 BETTER AND AFTER THAT THE 1672 01:19:14,755 --> 01:19:17,992 CONSEQUENCES CLUSTER AND THEN 1673 01:19:17,992 --> 01:19:20,661 THE NOT-HRD CLUSTER HAVING THE 1674 01:19:20,661 --> 01:19:22,663 WORSE OCCURRENCE FOR SURVIVAL. 1675 01:19:22,663 --> 01:19:24,798 AND THAT'S CONSISTENT WITH WHAT 1676 01:19:24,798 --> 01:19:27,268 HAS BEEN SEEN IN THE PUBLISHED 1677 01:19:27,268 --> 01:19:31,005 LITERATURE FOR INHIBITORS AND 1678 01:19:31,005 --> 01:19:33,007 THE SEVERITY OF CANCER BRCA 1679 01:19:33,007 --> 01:19:34,808 CLUSTER TENDS TO DO BEST AND THE 1680 01:19:34,808 --> 01:19:37,845 HRD CLUSTER THAT IS NOT BRCA 1681 01:19:37,845 --> 01:19:41,382 NEXT AND THE NOT HRD CLUSTER. 1682 01:19:41,382 --> 01:19:43,517 AND SIMILARLY LOOKING AT OVER 1683 01:19:43,517 --> 01:19:45,853 ALL SURVIVAL WE HAD A SIMILAR 1684 01:19:45,853 --> 01:19:49,890 TREND WHERE BRCA AND CLUSTERS 1685 01:19:49,890 --> 01:19:54,461 DID BETTER THAN NON-HRD CLUSTERS 1686 01:19:54,461 --> 01:19:55,996 AND THE SURVIVAL CURVES 1687 01:19:55,996 --> 01:19:58,899 INTERSECTED HERE AND AT THE END 1688 01:19:58,899 --> 01:20:00,701 OF THE DAY IT WAS NOT 1689 01:20:00,701 --> 01:20:02,436 SIGNIFICANT AND THE BRCA CLUSTER 1690 01:20:02,436 --> 01:20:05,005 HAD A WORSE MEDIAN OVER ALL 1691 01:20:05,005 --> 01:20:06,073 SURVIVAL BUT THE TREND WAS IN 1692 01:20:06,073 --> 01:20:09,810 THE RIGHT DIRECTION. 1693 01:20:09,810 --> 01:20:10,344 SIMILARLY WE LOOKED AT 1694 01:20:10,344 --> 01:20:13,380 INDIVIDUAL LABS AND YOU CAN SEE 1695 01:20:13,380 --> 01:20:15,916 THEY'RE KIND OF ALL OVER THE 1696 01:20:15,916 --> 01:20:16,650 PLACE HERE. 1697 01:20:16,650 --> 01:20:17,785 SOME LABS THERE'S NO SEPARATION 1698 01:20:17,785 --> 01:20:21,121 OCCURS BUT FOR SOME OF THE 1699 01:20:21,121 --> 01:20:22,756 ASSAYS, THERE'S ACTUALLY VERY 1700 01:20:22,756 --> 01:20:24,358 GOOD SEPARATION PARTICULARLY FOR 1701 01:20:24,358 --> 01:20:27,461 THE OVER ALL SURVIVAL DATA. 1702 01:20:27,461 --> 01:20:30,764 SO WHAT DOES THIS ALL TELL US? 1703 01:20:30,764 --> 01:20:35,736 I THINK THE LEVEL OF AGREEMENT 1704 01:20:35,736 --> 01:20:39,173 BETWEEN DIFFERENT ASSAYS VARY. 1705 01:20:39,173 --> 01:20:42,476 I THINK OVER ALL IT WAS A LITTLE 1706 01:20:42,476 --> 01:20:44,979 ALARMING IT WAS HIGHER THAN IT 1707 01:20:44,979 --> 01:20:45,279 WAS. 1708 01:20:45,279 --> 01:20:46,747 I THINK -- I HOPE YOU'RE HAVING 1709 01:20:46,747 --> 01:20:49,683 THE SAME REACTION TO IT WE ALL 1710 01:20:49,683 --> 01:20:51,719 DID IN THE HRD GROUP. 1711 01:20:51,719 --> 01:20:55,956 BUT I THINK SOME OF THAT CAN BE 1712 01:20:55,956 --> 01:20:57,591 EXPLAINED BY THE PAIRS OF ASSAYS 1713 01:20:57,591 --> 01:20:58,425 BEING COMPARED. 1714 01:20:58,425 --> 01:21:00,461 I TRIED TO GET INTO THAT A 1715 01:21:00,461 --> 01:21:01,362 LITTLE BIT. 1716 01:21:01,362 --> 01:21:07,101 IF YOU COMPARE A LAB'S ASSAY AND 1717 01:21:07,101 --> 01:21:08,202 THEY'RE DOING GENOMIC SCARRING 1718 01:21:08,202 --> 01:21:10,270 WITH AN ASSAY THAT DOESN'T 1719 01:21:10,270 --> 01:21:13,507 INCORPORATE THE SCARS AND MAYBE 1720 01:21:13,507 --> 01:21:19,346 JUST LOOKS AT HR REPAIR 1721 01:21:19,346 --> 01:21:20,848 MUTATIONS THERE'LL BE MORE 1722 01:21:20,848 --> 01:21:22,916 MUTATIONS THAN ONE SCARRING TO 1723 01:21:22,916 --> 01:21:23,984 ANOTHER. 1724 01:21:23,984 --> 01:21:25,853 THAT'S FAIR. 1725 01:21:25,853 --> 01:21:29,623 THAT'S STILL PERHAPS MORE 1726 01:21:29,623 --> 01:21:34,528 DISORDERAN ANAN ANAN ANANCE -- 1727 01:21:34,528 --> 01:21:35,963 YOU'D EXPECT TO SEE AND ABOUT 1728 01:21:35,963 --> 01:21:38,499 THE CHARACTERISTICS, WE DIDN'T 1729 01:21:38,499 --> 01:21:41,802 SEE ANY CORRELATION WITH THE 1730 01:21:41,802 --> 01:21:43,904 SAMPLE CHARACTERISTICS AND 1731 01:21:43,904 --> 01:21:45,039 CONCORDANCE BUT THEN AGAIN WE 1732 01:21:45,039 --> 01:21:48,409 RESTRICT THE STUDY TO SAMPLES 1733 01:21:48,409 --> 01:21:50,077 THAT WERE OF HIGHER QUALITY. 1734 01:21:50,077 --> 01:21:52,413 AND THEN FINALLY SOMETHING I 1735 01:21:52,413 --> 01:21:58,018 DIDN'T MENTION WAS THAT IT WOULD 1736 01:21:58,018 --> 01:22:02,656 HAVE BEEN NICE TO HAVE DONE AN 1737 01:22:02,656 --> 01:22:03,290 ANALYSIS STRATIFIED BASED ON 1738 01:22:03,290 --> 01:22:05,659 TREATMENT WITH AN INHIBITOR. 1739 01:22:05,659 --> 01:22:08,228 COULDN'T DO THAT BECAUSE THE 1740 01:22:08,228 --> 01:22:09,563 PATIENTS RETREATED BEFORE THEY 1741 01:22:09,563 --> 01:22:12,633 BECAME STANDARD OF CARE IN THE 1742 01:22:12,633 --> 01:22:14,435 MAINTENANCE SETTING AND ONLY 15 1743 01:22:14,435 --> 01:22:16,703 PATIENTS RECEIVED PART THAT WAS 1744 01:22:16,703 --> 01:22:18,305 AN ANALYSIS WE COULD NOT DO. 1745 01:22:18,305 --> 01:22:21,375 IN TERMS OF RECOMMENDATIONS FOR 1746 01:22:21,375 --> 01:22:25,145 THE FUTURE, WHAT IS THE BEST 1747 01:22:25,145 --> 01:22:26,547 APPROACH TO RECORD HRD. 1748 01:22:26,547 --> 01:22:28,882 IF WE COULD ALL ALIGN ON THAT, 1749 01:22:28,882 --> 01:22:31,318 THAT CONSISTENCY I DON'T KNOW 1750 01:22:31,318 --> 01:22:34,688 THAT WE KNOW THAT RIGHT NOW. 1751 01:22:34,688 --> 01:22:38,525 AND IT WOULD BE GOOD AS A FOLLOW 1752 01:22:38,525 --> 01:22:40,294 UP TO HAVE A COMMITTEE PERHAPS 1753 01:22:40,294 --> 01:22:43,797 CONVENE AND DISCUSS THAT. 1754 01:22:43,797 --> 01:22:45,365 IN TERMS OF TRYING TO VALIDATE 1755 01:22:45,365 --> 01:22:46,867 ASSAYS WE NEED TO RELY ON 1756 01:22:46,867 --> 01:22:49,837 EXPECTATIONS FOR HOW WE'RE GOING 1757 01:22:49,837 --> 01:22:51,338 TO DO THAT. 1758 01:22:51,338 --> 01:22:54,108 THESE ARE COMPLEX BIOMARKERS. 1759 01:22:54,108 --> 01:22:57,311 IT'S NOT TRIVIAL THINKING HOW TO 1760 01:22:57,311 --> 01:22:58,445 VALIDATE THEM AND THEN WE DON'T 1761 01:22:58,445 --> 01:23:00,247 HAVE A GOLD STANDARD. 1762 01:23:00,247 --> 01:23:01,782 I MENTIONED THAT SEVERAL TIMES. 1763 01:23:01,782 --> 01:23:06,820 SO IT WOULD BE NICE TO HAVE A 1764 01:23:06,820 --> 01:23:10,757 BIOLOGICAL GOLD STANDARD 1765 01:23:10,757 --> 01:23:15,028 INCLUDING REFERENCE MATERIALS 1766 01:23:15,028 --> 01:23:18,532 AND THE IN SILICO DATA COULD BE 1767 01:23:18,532 --> 01:23:19,867 USED FOR ASSAY DEVELOPMENT. 1768 01:23:19,867 --> 01:23:21,001 SO I JUST WANT TO THANK 1769 01:23:21,001 --> 01:23:22,769 EVERYBODY WHO PARTICIPATED IN 1770 01:23:22,769 --> 01:23:28,976 THE PARTICULARLY HILARY A 1771 01:23:28,976 --> 01:23:34,181 AND-DRANDREWS 1772 01:23:34,181 --> 01:23:35,282 AND REBECCA OREN FROM THE 1773 01:23:35,282 --> 01:23:37,451 UNIVERSITY OF ALABAMA. 1774 01:23:37,451 --> 01:23:40,053 FOLKS IN OUR LAB AND LILLY CHEN 1775 01:23:40,053 --> 01:23:46,760 AND LISA CHAPMAN AND I ALSO WANT 1776 01:23:46,760 --> 01:23:49,129 TO THANK FOR SUPPORT AND WE'RE 1777 01:23:49,129 --> 01:23:50,731 GRATEFUL TO HAVE THE SUPPORT. 1778 01:23:50,731 --> 01:24:00,908 THANK YOU. 1779 01:24:02,576 --> 01:24:06,547 >> THANK YOU. 1780 01:24:06,547 --> 01:24:08,949 QUESTIONS FROM THE GROUP. 1781 01:24:08,949 --> 01:24:09,416 ARE 1782 01:24:09,416 --> 01:24:12,519 >> HI, I'M FROM WASHINGTON 1783 01:24:12,519 --> 01:24:14,421 UNIVERSITY IN ST. LOUIS. 1784 01:24:14,421 --> 01:24:16,190 I LEAD AN OVARIAN CANCER GROUP 1785 01:24:16,190 --> 01:24:18,192 AND A MEMBER OF OUR GROUP 1786 01:24:18,192 --> 01:24:20,827 RECENTLY FUNCTIONED ON 1787 01:24:20,827 --> 01:24:22,462 FUNCTIONAL ASSAY FOR HRD USING 1788 01:24:22,462 --> 01:24:23,697 RAD 51 FOSI. 1789 01:24:23,697 --> 01:24:25,232 I WAS THINKING YOU WERE TALKING 1790 01:24:25,232 --> 01:24:26,600 ABOUT THE CAUSES AND 1791 01:24:26,600 --> 01:24:28,835 CONSEQUENCES AND SO THE GENOMIC 1792 01:24:28,835 --> 01:24:35,375 SCAR IS JUST A SNAPSHOT AND SO 1793 01:24:35,375 --> 01:24:36,210 WE'RE WONDERING IF YOU COULD 1794 01:24:36,210 --> 01:24:39,580 HAVE A REAL TIME OR FUNCTIONAL 1795 01:24:39,580 --> 01:24:41,448 ASSAY WITH ZERO BIOPSY OR 1796 01:24:41,448 --> 01:24:46,753 SOMETHING LIKE THAT EITHER FROM 1797 01:24:46,753 --> 01:24:49,423 LIQUID BIOPSY OR FROM THE ACTUAL 1798 01:24:49,423 --> 01:24:50,157 TISSUE. 1799 01:24:50,157 --> 01:24:52,326 SHE SHOWED REALLY NICELY AND 1800 01:24:52,326 --> 01:24:55,629 RECENTLY PUBLISHED IN CANCER 1801 01:24:55,629 --> 01:25:02,669 RESEARCH RAD 51 FOSI COULD BE A 1802 01:25:02,669 --> 01:25:05,339 FUNCTI 1803 01:25:05,339 --> 01:25:06,540 FUNCTI 1804 01:25:06,540 --> 01:25:08,508 FUNCTIONAL MARKER OF HRD AND 1805 01:25:08,508 --> 01:25:10,744 WONDER IF THAT CAME UP IN YOUR 1806 01:25:10,744 --> 01:25:11,311 DISCUSSIONS. 1807 01:25:11,311 --> 01:25:12,913 >> WE DIDN'T AND AT FREDERICK 1808 01:25:12,913 --> 01:25:18,552 NATIONAL LAB WE CAN INTERROGATE 1809 01:25:18,552 --> 01:25:22,122 RAD 51 FOSI. 1810 01:25:22,122 --> 01:25:27,160 I THINK IT WOULD BE INTERESTING 1811 01:25:27,160 --> 01:25:28,795 TO COMPARE THAT ASSAY TO SOME OF 1812 01:25:28,795 --> 01:25:33,900 THE ONES TALKED ABOUT AND THE 1813 01:25:33,900 --> 01:25:35,402 GENOMIC SCARS. 1814 01:25:35,402 --> 01:25:37,871 WILL THEY'RE FINE IN THE 1815 01:25:37,871 --> 01:25:38,672 TREATMENT NAIVE SETTING. 1816 01:25:38,672 --> 01:25:40,307 ONCE PATIENTS HAVE BEEN TREATED 1817 01:25:40,307 --> 01:25:42,042 AND DEVELOPED RESISTANCE THE 1818 01:25:42,042 --> 01:25:45,379 SCARS DON'T GO AWAY AND THEY'RE 1819 01:25:45,379 --> 01:25:46,446 NOT GOOD PREDICTION OF 1820 01:25:46,446 --> 01:25:48,015 BIOMARKERS AND YOU MENTIONED RAD 1821 01:25:48,015 --> 01:25:51,518 51 FOSI IN REAL TIME MEASURING 1822 01:25:51,518 --> 01:25:54,521 THE ABILITY OF CELLS IN REAL 1823 01:25:54,521 --> 01:25:55,389 TIME TO PERFORM EFFICIENT DNA 1824 01:25:55,389 --> 01:25:59,493 REPAIR IS A BETTER WAY TO GO IN 1825 01:25:59,493 --> 01:26:00,827 A PRETREATED POPULATION. 1826 01:26:00,827 --> 01:26:02,863 WE DIDN'T DO THAT COMPARISON. 1827 01:26:02,863 --> 01:26:05,165 I'D BE CURIOUS TO KNOW IF YOU OR 1828 01:26:05,165 --> 01:26:07,301 ANYBODY ELSE HAS DONE THAT AND 1829 01:26:07,301 --> 01:26:11,171 HAS DATA I WOULD IMAGINE -- 1830 01:26:11,171 --> 01:26:12,572 >> WELL, THAT'S THE NEXT STEP 1831 01:26:12,572 --> 01:26:16,043 WE'RE LOOKING AT SAMPLES FROM 1832 01:26:16,043 --> 01:26:17,878 PATIENTS TREATED WITH CAR 1833 01:26:17,878 --> 01:26:19,346 INHIBITORS AND WE'RE REPEATING 1834 01:26:19,346 --> 01:26:24,384 THE ASSAY AND THE FIRST IS MARY 1835 01:26:24,384 --> 01:26:28,221 MULLEN, M-U-L-L-E-N. 1836 01:26:28,221 --> 01:26:30,057 >> THANK YOU FOR THAT. 1837 01:26:30,057 --> 01:26:34,161 >> THIS IS TIM CHAN. 1838 01:26:34,161 --> 01:26:35,562 VERY NICE PRESENTATION AND 1839 01:26:35,562 --> 01:26:37,798 CONGRATULATIONS TO YOU AND YOUR 1840 01:26:37,798 --> 01:26:39,700 TEAM FOR DOING THAT VERY 1841 01:26:39,700 --> 01:26:41,601 ITERATIVE WORK BUT VERY 1842 01:26:41,601 --> 01:26:41,868 IMPORTANT. 1843 01:26:41,868 --> 01:26:44,938 SO MY QUESTION HERE IS I'M 1844 01:26:44,938 --> 01:26:46,340 CURIOUS OVER THE LAST YEAR OR 1845 01:26:46,340 --> 01:26:48,442 TWO ESPECIALLY AS A PUBLICATIONS 1846 01:26:48,442 --> 01:26:53,747 HAVE RULED OUT WHETHER YOU HAVE 1847 01:26:53,747 --> 01:26:56,550 SEEN ALL THE VARIOUS COMPANIES 1848 01:26:56,550 --> 01:26:59,252 WORKING ON TMB AND THE ACTIVITY 1849 01:26:59,252 --> 01:27:02,356 AT THE FDA WHETHER THERE HAS 1850 01:27:02,356 --> 01:27:06,293 BEEN CONNECTIONS WITH YOU TO 1851 01:27:06,293 --> 01:27:08,695 HARMONIZE AMONGST THE VARIOUS 1852 01:27:08,695 --> 01:27:14,434 ASSETS FOLKS HAVE IN DIAGNOSTICS 1853 01:27:14,434 --> 01:27:16,770 AND WITH THE FDA IN SOME FORM OR 1854 01:27:16,770 --> 01:27:19,973 FASHION TO TRY TO PUSH FORWARD A 1855 01:27:19,973 --> 01:27:21,375 WORK FLOW FOR HARMONIZATION. 1856 01:27:21,375 --> 01:27:23,143 I THINK IN THE LAST 10 YEARS 1857 01:27:23,143 --> 01:27:24,811 AFTER THE DISCOVERIES AND SO 1858 01:27:24,811 --> 01:27:30,617 FORTH, ONE OF THE CHALLENGES HAS 1859 01:27:30,617 --> 01:27:33,887 BEEN THE FIELD AND PUTTING 1860 01:27:33,887 --> 01:27:36,623 TOGETHER METHODS EVERYBODY 1861 01:27:36,623 --> 01:27:38,759 ACCEPTS RATHER THAN CONTINUED 1862 01:27:38,759 --> 01:27:40,260 COMPETING DIAGNOSTICS. 1863 01:27:40,260 --> 01:27:44,498 >> YEAH, THANKS FOR THAT, TIM. 1864 01:27:44,498 --> 01:27:46,099 THOSE ARE GREAT POINTS. 1865 01:27:46,099 --> 01:27:50,670 I'M NOT AWARE OF CONVERSATIONS 1866 01:27:50,670 --> 01:27:54,174 THAT HAVE BEEN HAD WITH FDA BY 1867 01:27:54,174 --> 01:27:55,075 MEMBERS OF THE FRIENDS 1868 01:27:55,075 --> 01:27:57,611 CONSORTIUM ON THE PROJECT. 1869 01:27:57,611 --> 01:27:59,212 I MENTIONED THE PROJECT DREW TO 1870 01:27:59,212 --> 01:28:01,014 A CLOSE BACK IN 2020, 2021, I 1871 01:28:01,014 --> 01:28:05,652 THINK. 1872 01:28:05,652 --> 01:28:10,190 I'D BE CURIOUS TO KNOW THE GOLD 1873 01:28:10,190 --> 01:28:12,526 STANDARD FDA IS USING WHEN A 1874 01:28:12,526 --> 01:28:14,294 SPONSOR COMES WITH AN ASSAY THEY 1875 01:28:14,294 --> 01:28:24,571 WANT TO GET APPROVAL FOR. 1876 01:28:24,571 --> 01:28:26,640 DO THEY EXPECT THE SUBMITTER TO 1877 01:28:26,640 --> 01:28:32,446 HAVE AN ACCURACY STUDY THEY 1878 01:28:32,446 --> 01:28:34,281 PERFORMED OR SENSITIVITY STUDY 1879 01:28:34,281 --> 01:28:35,348 PERFORMED WITH FOUNDATION 1880 01:28:35,348 --> 01:28:40,687 MEDICINE AS THE GOLD STANDARD OR 1881 01:28:40,687 --> 01:28:42,856 WOULD IT BE MORE APPROPRIATE TO 1882 01:28:42,856 --> 01:28:45,992 THINK ABOUT A CALIBRATOR 1883 01:28:45,992 --> 01:28:50,730 APPROACH LIKE I WAS DESCRIBING 1884 01:28:50,730 --> 01:28:54,701 TO MAYBE ADJUST TMB VALUES TO A 1885 01:28:54,701 --> 01:28:57,437 WEST STANDARD. 1886 01:28:57,437 --> 01:28:59,105 THAT WOULD BE MY PREFERENCE 1887 01:28:59,105 --> 01:28:59,372 ACTUALLY. 1888 01:28:59,372 --> 01:29:01,908 I HONESTLY DON'T KNOW WHERE THIS 1889 01:29:01,908 --> 01:29:03,210 HAS GONE. 1890 01:29:03,210 --> 01:29:07,247 WE WORK WITH FRIENDS ALL THE 1891 01:29:07,247 --> 01:29:07,514 TIME. 1892 01:29:07,514 --> 01:29:08,815 I'LL ASK THEM IF THEY'VE HAD 1893 01:29:08,815 --> 01:29:10,750 FURTHER CONVERSATIONS WITH FDA 1894 01:29:10,750 --> 01:29:12,652 BUT I'M NOT AWARE OF ANY. 1895 01:29:12,652 --> 01:29:15,155 >> TERRIFIC, THREW. 1896 01:29:15,155 --> 01:29:18,658 -- TERRIFIC, THANK YOU. 1897 01:29:18,658 --> 01:29:24,798 >> ANY OTHER QUESTIONS? 1898 01:29:24,798 --> 01:29:25,031 OKAY. 1899 01:29:25,031 --> 01:29:29,202 THANK YOU, CHRIS. 1900 01:29:29,202 --> 01:29:30,036 FOR AN INTRIGUING CONVERSATION 1901 01:29:30,036 --> 01:29:32,672 AND WE'RE TAKING A BREAK NOW 1902 01:29:32,672 --> 01:29:33,573 UNTIL 2:50. 1903 01:29:33,573 --> 01:29:36,009 DOES THAT WORK FOR EVERYBODY? 1904 01:29:36,009 --> 01:29:38,678 PLEASE TRY AND BE BACK A LITTLE 1905 01:29:38,678 --> 01:29:40,981 BIT EARLY SO WE MAKE SURE TO 1906 01:29:40,981 --> 01:29:42,382 START RIGHT ON TIME AND HEAR 1907 01:29:42,382 --> 01:29:44,733 FROM DR. McCORMICK ON RAS AFTER THE BREAK. 1908 01:29:44,733 --> 01:29:46,001 WELCOME BACK, EVERYBODY. 1909 01:29:46,001 --> 01:29:50,739 DR. McCORMICK IS GOING TO TALK 1910 01:29:50,739 --> 01:29:57,446 TO US. 1911 01:29:57,446 --> 01:29:57,679 PLEASE. 1912 01:29:57,679 --> 01:29:59,047 >> WANT TO HEAR ABOUT RAS? 1913 01:29:59,047 --> 01:30:02,717 >> YES, WE DO. 1914 01:30:02,717 --> 01:30:04,219 >> GREAT. 1915 01:30:04,219 --> 01:30:05,954 I'M HAPPY TO GIVE YOU UPDATES ON 1916 01:30:05,954 --> 01:30:06,521 OUR PROGRAM. 1917 01:30:06,521 --> 01:30:08,223 WHAT I'M GOING TO DO TODAY IS 1918 01:30:08,223 --> 01:30:14,096 FOCUS ON TWO ASPECTS OF THE RAS 1919 01:30:14,096 --> 01:30:15,597 INITIATIVES THE COMPOUNDS IN THE 1920 01:30:15,597 --> 01:30:17,699 CLINIC OR HEADING TO THE CLINIC. 1921 01:30:17,699 --> 01:30:23,238 FOR US THESE ARE MAJOR 1922 01:30:23,238 --> 01:30:23,972 MILESTONES. 1923 01:30:23,972 --> 01:30:29,077 TO BE ABLE TO SAY WE HAVE THESE 1924 01:30:29,077 --> 01:30:30,679 IS HUGE AND WE'RE PROUD OF OUR 1925 01:30:30,679 --> 01:30:32,848 TEAM AND WANT TO SHARE HOW THE 1926 01:30:32,848 --> 01:30:34,583 COMPOUNDS WORK, WHY THEY'RE 1927 01:30:34,583 --> 01:30:39,454 DIFFERENT FROM OTHER COMPOUNDS 1928 01:30:39,454 --> 01:30:41,056 AHEAD OF US AND WHAT WE EXPECT 1929 01:30:41,056 --> 01:30:42,591 IN THE FUTURE. 1930 01:30:42,591 --> 01:30:46,728 THE FIRST COUNT IS 8520 THAT 1931 01:30:46,728 --> 01:30:50,398 HITS THE G12C OR K RAS PROTEIN 1932 01:30:50,398 --> 01:30:51,933 IN THE ACTIVE STATE THEREFORE 1933 01:30:51,933 --> 01:30:52,934 DIFFERENT FROM THE OTHER 1934 01:30:52,934 --> 01:30:57,839 COMPOUNDS AS I'LL SHOW. 1935 01:30:57,839 --> 01:30:59,574 IT'S BEEN IN PHASE I CLINICAL 1936 01:30:59,574 --> 01:31:03,712 TRIALS AND TESTED AT FOUR SITES 1937 01:31:03,712 --> 01:31:05,313 IN THE U.S. AND TWO IN AUSTRALIA 1938 01:31:05,313 --> 01:31:09,451 FOR REASONS I CAN GET BACK TO 1939 01:31:09,451 --> 01:31:13,021 LATER AND THE SECOND COMPOUND IS 1940 01:31:13,021 --> 01:31:15,624 SOMETHING DIFFERENT. 1941 01:31:15,624 --> 01:31:19,628 A COMPOUND DRUG THAT BINDS AND 1942 01:31:19,628 --> 01:31:21,163 PREVENTS ALPHA PROTEINS AND THIS 1943 01:31:21,163 --> 01:31:28,270 IS A NOVEL WAY OF INHIBITING THE 1944 01:31:28,270 --> 01:31:30,105 KINASE ACTIVITY IN CELLS IN 1945 01:31:30,105 --> 01:31:31,473 COMBINATION WITH OTHER DRUGS 1946 01:31:31,473 --> 01:31:34,709 WITHOUT THE PENALTY OR LIABILITY 1947 01:31:34,709 --> 01:31:36,811 OF INDUCING HYPERGLYCEMIA THE 1948 01:31:36,811 --> 01:31:41,383 PROBLEM WITH OTHER INHIBITORS. 1949 01:31:41,383 --> 01:31:42,584 SO YOU'RE PROBABLY ALL PROBABLY 1950 01:31:42,584 --> 01:31:44,119 SICK OF SEEING THE PATHWAY BUT 1951 01:31:44,119 --> 01:31:46,154 THIS IS TO REMIND YOU WHY OUR 1952 01:31:46,154 --> 01:31:46,821 APPROACH IS DIFFERENT FROM THE 1953 01:31:46,821 --> 01:31:50,458 OTHER APPROACHES. 1954 01:31:50,458 --> 01:31:55,030 AGAIN YOU ALL KNOW UP CELLS, RAS 1955 01:31:55,030 --> 01:32:00,802 PROTEIN CYCLE BETWEEN THE GTP 1956 01:32:00,802 --> 01:32:05,273 AND GDP STATE. 1957 01:32:05,273 --> 01:32:09,044 BECAUSE PROTEIN C12C AND B AND D 1958 01:32:09,044 --> 01:32:11,713 ARE RESISTANT TO GAPS THEY 1959 01:32:11,713 --> 01:32:14,449 ACCUMULATE IN THE G BOND STATE 1960 01:32:14,449 --> 01:32:14,950 MALIGNANT PROPERTIES. 1961 01:32:14,950 --> 01:32:16,551 SO THE CHALLENGE HAS BEEN HOW TO 1962 01:32:16,551 --> 01:32:18,520 FIND COMPOUNDS THAT BIND TO 1963 01:32:18,520 --> 01:32:20,989 THESE PROTEINS AND BLOCK THE 1964 01:32:20,989 --> 01:32:22,657 DOWN STREAM SIGNALLING. 1965 01:32:22,657 --> 01:32:26,695 THE NEXT SLIDE HIGHLIGHTS THE 1966 01:32:26,695 --> 01:32:28,697 POINT OF INTERVENTION OF THE 1967 01:32:28,697 --> 01:32:33,168 APPROVED 12C INHIBITORS AS WELL 1968 01:32:33,168 --> 01:32:34,135 AS ANOTHER 10 COMPOUNDS WHICH 1969 01:32:34,135 --> 01:32:36,271 ARE SIMILAR IN MANY WAYS TO THE 1970 01:32:36,271 --> 01:32:37,739 TWO PIONEERING COMPOUNDS. 1971 01:32:37,739 --> 01:32:39,274 THE TWO ON THE SIDE HERE HAVE 1972 01:32:39,274 --> 01:32:39,841 ALREADY BEEN APPROVED FOR 1973 01:32:39,841 --> 01:32:49,985 THERAPY. 1974 01:32:50,785 --> 01:32:53,188 THEY IS SCREENED THE LIBRARY AND 1975 01:32:53,188 --> 01:32:55,023 FOUND A NUMBER OF HITS WHEN 1976 01:32:55,023 --> 01:32:58,960 SCREENED WITH A GDP FORM OF G12C 1977 01:32:58,960 --> 01:33:02,664 BUT NO HIS WITH THE GTP BOUND 1978 01:33:02,664 --> 01:33:02,864 FORM. 1979 01:33:02,864 --> 01:33:06,701 HE AND OTHERS HAVE CONCLUDED THE 1980 01:33:06,701 --> 01:33:07,769 WILL POCKET IS ONLY AVAILABLE 1981 01:33:07,769 --> 01:33:12,741 FOR CO-VALENT FINDING IN THE GDP 1982 01:33:12,741 --> 01:33:13,174 COMPOUND STATE. 1983 01:33:13,174 --> 01:33:14,609 SO THEY'RE THE OFF STATE NOT THE 1984 01:33:14,609 --> 01:33:15,310 ON STATE. 1985 01:33:15,310 --> 01:33:23,285 THE FEATURE OF TRAPPING IT. 1986 01:33:23,285 --> 01:33:25,787 IT SOUND LIKE AN ATTRACTIVE 1987 01:33:25,787 --> 01:33:27,722 METHOD FOR SHUTTING DOWN RAS 1988 01:33:27,722 --> 01:33:29,057 SIGNALLING. 1989 01:33:29,057 --> 01:33:31,226 THE CLINICAL RESPONSES TO THE 1990 01:33:31,226 --> 01:33:33,662 COMPOUNDS HAVE NOT BEEN VERY 1991 01:33:33,662 --> 01:33:33,928 DURABLE. 1992 01:33:33,928 --> 01:33:35,764 IT'S RELATIVELY EASY FOR THE 1993 01:33:35,764 --> 01:33:37,499 TUMOR CELL TO ESCAPE FROM THE 1994 01:33:37,499 --> 01:33:39,567 TRAP EITHER BY PUMPING MORE 1995 01:33:39,567 --> 01:33:42,404 SIGNALS DOWN THE PATHWAY FROM 1996 01:33:42,404 --> 01:33:43,405 GROWTH FACTORS TO POWER THROUGH 1997 01:33:43,405 --> 01:33:46,107 INTO THE ACTIVE STATE OR SIMPLY 1998 01:33:46,107 --> 01:33:48,977 BY MAKING MORE K RAS SO THE DRUG 1999 01:33:48,977 --> 01:33:52,380 CAN'T KEEP UP AND TRAP IT IN THE 2000 01:33:52,380 --> 01:33:57,419 INACTIVE STATE AND THOSE ARE TWO 2001 01:33:57,419 --> 01:33:57,819 MECHANISMS. 2002 01:33:57,819 --> 01:34:01,056 THE UPSTREAM SIGNALLING AND OVER 2003 01:34:01,056 --> 01:34:02,157 EXPRESSION OF K RAS. 2004 01:34:02,157 --> 01:34:04,426 SO OUR APPROACH FROM THE 2005 01:34:04,426 --> 01:34:05,960 BEGINNING OF THE INITIATIVE 2006 01:34:05,960 --> 01:34:07,162 TARGETING THE ACTIVE FORM OF THE 2007 01:34:07,162 --> 01:34:16,171 RAS PROTEIN. 2008 01:34:16,171 --> 01:34:19,040 THIS PRECEDED OUR APPROACH TO 2009 01:34:19,040 --> 01:34:22,110 G12C AND FELT THE HITTING THE G 2010 01:34:22,110 --> 01:34:23,278 POUND FORM WOULD BE MORE 2011 01:34:23,278 --> 01:34:25,213 EFFECTIVE NOT REALIZING HOW HARD 2012 01:34:25,213 --> 01:34:26,948 IT WOULD BE TO FIND COMPOUND 2013 01:34:26,948 --> 01:34:30,151 THAT BIND IN THAT POCKET WHERE 2014 01:34:30,151 --> 01:34:31,519 OTHER COMPOUND SQUEEZE IN. 2015 01:34:31,519 --> 01:34:34,756 WE SPENT MANY YEARS TARGETING 2016 01:34:34,756 --> 01:34:38,727 THE DIFFERENT RAS ALLELES AND 2017 01:34:38,727 --> 01:34:40,028 COMBINED OUR EXPERIENCE WITH 2018 01:34:40,028 --> 01:34:41,529 OTHERS TARGETING G COMPOUNDS TO 2019 01:34:41,529 --> 01:34:44,733 BUILD COMPOUND THAT IS ABLE TO 2020 01:34:44,733 --> 01:34:47,102 BIND TO THE GTP BOUND FORM AND 2021 01:34:47,102 --> 01:34:50,572 PREVENT DOWN STREAM SIGNALLING. 2022 01:34:50,572 --> 01:34:52,741 THIS TOOK YEARS OF ADDITIONAL 2023 01:34:52,741 --> 01:34:57,011 BIO CHEMISTRY AND STRUCTURAL 2024 01:34:57,011 --> 01:35:01,583 BIOLOGY WITH OUR CREATIVE 2025 01:35:01,583 --> 01:35:02,984 PARTNERS AND NATIONAL LAB BUT 2026 01:35:02,984 --> 01:35:04,285 EVENTUALLY WE FOUND A COMPOUND 2027 01:35:04,285 --> 01:35:06,121 THAT COULD SQUEEZE ITS WAY IN 2028 01:35:06,121 --> 01:35:10,291 THE GTP BOUND FORM EFFECTIVELY 2029 01:35:10,291 --> 01:35:12,227 AND BIND TO THE GTP AND GDP 2030 01:35:12,227 --> 01:35:18,700 BOUND FORM. 2031 01:35:18,700 --> 01:35:21,936 JUST TO INTRODUCE 8520 AND THE 2032 01:35:21,936 --> 01:35:25,240 TEAM ON THE RIGHT AT FREDERICK 2033 01:35:25,240 --> 01:35:26,441 NATIONAL LAB HEADED UP BY A 2034 01:35:26,441 --> 01:35:30,779 LARGE NUMBER OF INDIVIDUALS IN 2035 01:35:30,779 --> 01:35:35,016 THE RAS INITIATIVE WERE INVOLVED 2036 01:35:35,016 --> 01:35:36,651 AND THE PARTNERS AND 2037 01:35:36,651 --> 01:35:37,652 COLLABORATORS THAT PROVIDE A 2038 01:35:37,652 --> 01:35:41,189 GREAT DEAL OF MACHINE LEARNING 2039 01:35:41,189 --> 01:35:43,992 AND A.I. INPUT IN DRUG DESIGN. 2040 01:35:43,992 --> 01:35:45,493 THE PROBLEM WITH THE COMPOUND IS 2041 01:35:45,493 --> 01:35:48,430 SHOWN THERE. 2042 01:35:48,430 --> 01:35:51,933 IT INHIBITS KINASE POCKET 2043 01:35:51,933 --> 01:35:55,203 SIGNALLING AND VERY POTENT AND 2044 01:35:55,203 --> 01:35:57,272 HAS GREAT DRUG LAB PROPERTIES 2045 01:35:57,272 --> 01:35:59,674 AND WE THINK WILL BE WELL 2046 01:35:59,674 --> 01:35:59,941 TOLERATED. 2047 01:35:59,941 --> 01:36:02,043 WE'LL FIND OUT SOON. 2048 01:36:02,043 --> 01:36:06,714 THE BOTTOM LEFT PANEL SHOWS IT'S 2049 01:36:06,714 --> 01:36:09,651 POTENT AND IN PROTEOME ANALYSIS 2050 01:36:09,651 --> 01:36:12,587 THE ONLY PROTEIN IN THE CELL 2051 01:36:12,587 --> 01:36:16,691 THAT IT BINDS TO IS K RAS, G12C. 2052 01:36:16,691 --> 01:36:18,726 SO IT'S POTENT AND SPECIFIC AND 2053 01:36:18,726 --> 01:36:26,468 DOES HIT THE ACTIVE STATE. 2054 01:36:26,468 --> 01:36:28,403 SO THE OFF STATE TRAPPING 2055 01:36:28,403 --> 01:36:31,573 COMPOUND AS I MENTIONED HOLD THE 2056 01:36:31,573 --> 01:36:37,045 RAS PROTEIN IN THE INACTIVE 2057 01:36:37,045 --> 01:36:37,512 STATE. 2058 01:36:37,512 --> 01:36:39,481 YOU MIGHT ASK HOW DOES IT BIND 2059 01:36:39,481 --> 01:36:41,583 TO THE ACTIVE STATE PREVENT THE 2060 01:36:41,583 --> 01:36:41,916 SIGNALLING. 2061 01:36:41,916 --> 01:36:43,718 THE KEY TO UNDERSTANDING THIS 2062 01:36:43,718 --> 01:36:47,689 COMES FROM STRUCTURAL BIOLOGY 2063 01:36:47,689 --> 01:36:48,456 ANALYSIS FROM FREDERICK NATIONAL 2064 01:36:48,456 --> 01:36:52,126 LAB WITH A RANGE OF DIFFERENT 2065 01:36:52,126 --> 01:36:53,194 ONCOGENIC RAS PROTEINS. 2066 01:36:53,194 --> 01:36:55,864 AND THE IMPORTANT PART HERE IS 2067 01:36:55,864 --> 01:36:56,764 THAT SOME OF THESE STRUCTURES 2068 01:36:56,764 --> 01:37:00,301 LIKE THE ONE ON THE LEFT SHOW 2069 01:37:00,301 --> 01:37:01,870 THE SWITCH 1 REGION WHERE RAF 2070 01:37:01,870 --> 01:37:03,571 AND OTHER BIND IS OUT IN THE 2071 01:37:03,571 --> 01:37:09,544 WIND AWAY FROM THE D DOMAIN THE 2072 01:37:09,544 --> 01:37:11,746 BLUE STRETCH AND OTHER CRYSTAL 2073 01:37:11,746 --> 01:37:13,515 STRUCTURES IN THE MIDDLE WHERE 2074 01:37:13,515 --> 01:37:17,485 SWITCH 1 IS DOWN NOT G DOMAIN. 2075 01:37:17,485 --> 01:37:20,655 AND SOLVE THE STRUCTURE OF K RAS 2076 01:37:20,655 --> 01:37:23,258 BOUND TO THE EFFECT OF RAF YOU 2077 01:37:23,258 --> 01:37:26,728 CAN SEE SWITCH 1 IS IN THE STATE 2078 01:37:26,728 --> 01:37:29,764 2 CONFIGURATION AND DOES NOT 2079 01:37:29,764 --> 01:37:32,066 BIND TO RAF. 2080 01:37:32,066 --> 01:37:36,938 AS IT TURNS OUT IT SQUEEZES IN 2081 01:37:36,938 --> 01:37:40,174 THE POCKET AND PUSHES THIS INTO 2082 01:37:40,174 --> 01:37:40,575 STATE 1. 2083 01:37:40,575 --> 01:37:42,844 IT'S STILL GTP BOUND BUT CAN NO 2084 01:37:42,844 --> 01:37:44,646 LONGER ENGAGE EFFECTERS. 2085 01:37:44,646 --> 01:37:49,984 WE CAN ALSO ANALYZE IT THIS ON 2086 01:37:49,984 --> 01:37:55,356 THE NEXT SLIDE USING 2-D NMR 2087 01:37:55,356 --> 01:37:57,258 ANALYSIS SUMMARIZING A PAPER IN 2088 01:37:57,258 --> 01:38:00,094 THE BOTTOM OF THE SLIGHT. 2089 01:38:00,094 --> 01:38:03,231 A TECHNIQUE DEVISED YEARS AGO TO 2090 01:38:03,231 --> 01:38:05,600 MEASURE P31 WITH THE GTP. 2091 01:38:05,600 --> 01:38:06,901 YOU CAN TILL THE DIFFERENCE 2092 01:38:06,901 --> 01:38:09,971 BETWEEN GTP -- SORRY, STATE 1 2093 01:38:09,971 --> 01:38:12,040 AND STATE 2 BY THE RESIDENCE OF 2094 01:38:12,040 --> 01:38:14,208 THE GAMMA PHOSPHATE COMPARED TO 2095 01:38:14,208 --> 01:38:18,079 THE BOTTOM PANELS IN WHICH 2096 01:38:18,079 --> 01:38:20,982 PROTEIN IS TREATED WITH THE 2097 01:38:20,982 --> 01:38:22,517 COMPOUND WHY TRAPS IT IN THE 2098 01:38:22,517 --> 01:38:24,118 STATE 1 COMPARED TO THE 2099 01:38:24,118 --> 01:38:25,753 UNTREATED PROTEIN IN 2. 2100 01:38:25,753 --> 01:38:28,356 YOU CAN IMMEDIATELY TELL HOW THE 2101 01:38:28,356 --> 01:38:29,691 COMPOUND IS WORKING. 2102 01:38:29,691 --> 01:38:32,827 THIS WE CARRIED OVER INTO OUR 2103 01:38:32,827 --> 01:38:36,264 OTHER PROGRAMS TARGETING OTHER 2104 01:38:36,264 --> 01:38:37,865 ACTIVE ALLELES LEADING TO 2105 01:38:37,865 --> 01:38:39,400 COMPOUNDS WE HOPE HEADING TO THE 2106 01:38:39,400 --> 01:38:40,568 CLINIC NEXT YEAR BUT I WON'T BE 2107 01:38:40,568 --> 01:38:46,975 TALKING ABOUT THOSE TODAY. 2108 01:38:46,975 --> 01:38:50,511 THIS TRAPS THE GTP PROTEINS IN 2109 01:38:50,511 --> 01:38:52,714 THE STATE 1 MECHANISM FROM 2110 01:38:52,714 --> 01:38:56,150 LOCKING THE INACTIVE PROTEINS 2111 01:38:56,150 --> 01:39:04,525 WITH THE PREVIOUS COMPOUNDS. 2112 01:39:04,525 --> 01:39:05,693 BECAUSE WE'RE ABLE TO BIND 2113 01:39:05,693 --> 01:39:08,496 DIRECTLY TO THE GTP FORM WE 2114 01:39:08,496 --> 01:39:10,665 ENGAGE TARGET QUICKLY IN CELLS 2115 01:39:10,665 --> 01:39:14,702 AND SHUT DOWN RAS SIGNALLING 2116 01:39:14,702 --> 01:39:18,406 MORE RAPIDLY THAN WITH CLINICAL 2117 01:39:18,406 --> 01:39:19,140 CONCENTRATIONS OF COMPOUNDS AND 2118 01:39:19,140 --> 01:39:24,946 TAKE TIME TO CYCLE THROUGH AND 2119 01:39:24,946 --> 01:39:26,280 HIT THE RAF PROTEIN AND PREVENT 2120 01:39:26,280 --> 01:39:27,849 THE BINDING. 2121 01:39:27,849 --> 01:39:29,283 WE EXPECT TO GET MORE RAPID 2122 01:39:29,283 --> 01:39:31,686 RESPONSES AND DURABLE RESPONSES 2123 01:39:31,686 --> 01:39:36,424 BECAUSE FOR THIS COMPOUND HAVING 2124 01:39:36,424 --> 01:39:38,259 UPSTREAM SIGNALLING FEEDING RAS 2125 01:39:38,259 --> 01:39:40,428 GTP HELPS BIND THE TARGET RATHER 2126 01:39:40,428 --> 01:39:42,530 THAN IN HINDERS IT. 2127 01:39:42,530 --> 01:39:46,200 WE HOPE IN THE CLINIC WE'LL SEE 2128 01:39:46,200 --> 01:39:48,002 MORE RAPID AND MORE DRAMATIC 2129 01:39:48,002 --> 01:39:49,704 INITIAL RESPONSES AND MORE 2130 01:39:49,704 --> 01:39:52,840 DURABLE RESPONSES BECAUSE WE 2131 01:39:52,840 --> 01:39:54,742 WON'T GET RESISTANCE FROM UP 2132 01:39:54,742 --> 01:39:55,743 STREAM SIGNALLING OR EXPRESSION 2133 01:39:55,743 --> 01:39:58,713 OF K RAS. 2134 01:39:58,713 --> 01:39:59,914 THAT'S THE THEORY. 2135 01:39:59,914 --> 01:40:02,717 WE EXPECT MOST THE PATIENTS WILL 2136 01:40:02,717 --> 01:40:06,688 BE TREATING WILL HAVE SEEN THE 2137 01:40:06,688 --> 01:40:07,789 INHIBITOR AND WILL HAVE 2138 01:40:07,789 --> 01:40:11,092 PROGRESSED DUE TO THE TWO 2139 01:40:11,092 --> 01:40:11,392 MECHANISMS. 2140 01:40:11,392 --> 01:40:13,227 IN THE U.S. MOST THE PATIENTS 2141 01:40:13,227 --> 01:40:16,464 WILL BE PATIENTS PRETREATED BUT 2142 01:40:16,464 --> 01:40:18,533 IN AUSTRALIA IT'S POSSIBLE TO 2143 01:40:18,533 --> 01:40:21,602 FIND TREATMENTS WHO HAVEN'T BEEN 2144 01:40:21,602 --> 01:40:23,971 TREATED WITH ANY G12 COMPOUNDS 2145 01:40:23,971 --> 01:40:26,074 AND SOME WILL BE G12C NAIVE AND 2146 01:40:26,074 --> 01:40:27,875 MAY GET A RATING ON HOW 2147 01:40:27,875 --> 01:40:29,977 EFFECTIVELY THE DRUG WORKS ON 2148 01:40:29,977 --> 01:40:32,146 PATIENTS WHO HAVEN'T SEEN G12C 2149 01:40:32,146 --> 01:40:33,581 PREVIOUSLY IN THE COHORT IF WE 2150 01:40:33,581 --> 01:40:34,749 GET ENOUGH PATIENTS IN THE 2151 01:40:34,749 --> 01:40:42,757 COHORT. 2152 01:40:42,757 --> 01:40:44,592 AND IN TERMS OF ACCRUAL AND 2153 01:40:44,592 --> 01:40:55,069 RESPONSES AND PK AND SO ON. 2154 01:41:06,380 --> 01:41:07,248 WITH CAN GET WILL RESPONSES IN 2155 01:41:07,248 --> 01:41:11,052 THE MODELS. 2156 01:41:11,052 --> 01:41:12,987 WE'LL SEE HOW THINGS PAN OUT IN 2157 01:41:12,987 --> 01:41:13,287 THE CLINIC. 2158 01:41:13,287 --> 01:41:21,696 CLINICAL TRIALS ARE UNDERWAY. 2159 01:41:21,696 --> 01:41:25,199 THE OTHER APPROACH, THE IND HAS 2160 01:41:25,199 --> 01:41:26,367 BEEN CLEARED AND EXPECT TO START 2161 01:41:26,367 --> 01:41:27,869 TREATING IN THE NEXT MONTH OR 2162 01:41:27,869 --> 01:41:28,035 TWO. 2163 01:41:28,035 --> 01:41:29,470 THIS IS A DIFFERENT APPROACH. 2164 01:41:29,470 --> 01:41:30,471 THIS IS BASED ON OUR 2165 01:41:30,471 --> 01:41:32,106 UNDERSTANDING OF THINKING ABOUT 2166 01:41:32,106 --> 01:41:34,742 HOW RAS PROTEINS ARE ENROLLED IN 2167 01:41:34,742 --> 01:41:37,612 KINASE ACTIVATION. 2168 01:41:37,612 --> 01:41:40,948 SO ON THE LEFT PANEL I'LL SHOW A 2169 01:41:40,948 --> 01:41:43,551 DIAGRAM HOW INSULIN ACTIVATES 2170 01:41:43,551 --> 01:41:47,955 THE KINASE AND IS CRITICAL TO 2171 01:41:47,955 --> 01:41:50,291 UNDERSTANDING THE PROJECT. 2172 01:41:50,291 --> 01:41:52,126 INSULIN RECRUITS THE KINASE TO 2173 01:41:52,126 --> 01:42:02,670 THE RS1 THAT RECRUITS THE KINASE 2174 01:42:03,704 --> 01:42:09,143 AND INSULIN CAUSES CAUSE TO TAKE 2175 01:42:09,143 --> 01:42:11,345 UP GLUCOSE AND IT SHUT DOWN THE 2176 01:42:11,345 --> 01:42:12,613 PATHWAY AND THEREFORE PATIENTS 2177 01:42:12,613 --> 01:42:14,315 BEING TREATED WITH THOSE DRUGS 2178 01:42:14,315 --> 01:42:15,349 CANNOT TAKE UP GLUCOSE AND 2179 01:42:15,349 --> 01:42:18,753 SUFFER FROM ALL THE SIDE EFFECTS 2180 01:42:18,753 --> 01:42:23,090 OF HYPERGLYCEMIA. 2181 01:42:23,090 --> 01:42:26,661 AND OTHER KINASE LIKE PDP AND 2182 01:42:26,661 --> 01:42:28,563 EGF ALSO ACTIVATE THE KINASE 2183 01:42:28,563 --> 01:42:30,031 WITHOUT AN HELP FROM RAS. 2184 01:42:30,031 --> 01:42:32,400 WE KNOW IT'S TRUE AND ACTIVATE 2185 01:42:32,400 --> 01:42:33,100 THE PATHWAY WITHOUT ANY HELP 2186 01:42:33,100 --> 01:42:34,302 FROM RAS PROTEINS. 2187 01:42:34,302 --> 01:42:37,238 MOST OF THAT ACTIVITY IS RAS 2188 01:42:37,238 --> 01:42:39,540 INDEPENDENT. 2189 01:42:39,540 --> 01:42:41,776 HOWEVER, THE THIRD PANEL SHOWS 2190 01:42:41,776 --> 01:42:42,543 SOME CIRCUMSTANCES DURING 2191 01:42:42,543 --> 01:42:45,146 DEVELOPMENT IN MICE AT LEAST 2192 01:42:45,146 --> 01:42:48,916 DURING THE GENESIS RAS PROTEINS 2193 01:42:48,916 --> 01:42:51,285 CAN BE RECRUITED TO TRAP THE 2194 01:42:51,285 --> 01:42:52,854 KINASE ALPHA IN THE COMPLEX IN 2195 01:42:52,854 --> 01:42:56,157 THE MEMBRANE AND INCREASE SIGNAL 2196 01:42:56,157 --> 01:42:58,059 OUTPUT BECAUSE THE SUBSTRATE IS 2197 01:42:58,059 --> 01:43:02,697 IN A CLASS. 2198 01:43:02,697 --> 01:43:04,398 SO THE PRECISE ROLE IS NOT WELL 2199 01:43:04,398 --> 01:43:06,500 UNDERSTAND BUT GENETICS TELL US 2200 01:43:06,500 --> 01:43:08,803 SOME RAS PROTEINS ARE INVOLVED 2201 01:43:08,803 --> 01:43:10,872 IN ABNORMAL SIGNALLING THROUGH 2202 01:43:10,872 --> 01:43:12,206 RTKs. 2203 01:43:12,206 --> 01:43:18,646 IN THE FAR RIGHT WE KNOW 2204 01:43:18,646 --> 01:43:20,281 ONCOGENETIC RAS PROTEINS CAN 2205 01:43:20,281 --> 01:43:22,750 ACTIVATE IT IN THE SIGNALLING. 2206 01:43:22,750 --> 01:43:24,518 SO THE PANELS ARE THE ONES WE'LL 2207 01:43:24,518 --> 01:43:27,355 BE ADDRESSING WITH THE DRUG THAT 2208 01:43:27,355 --> 01:43:30,491 PREVENTS RAS ACTIVATING PF3 2209 01:43:30,491 --> 01:43:32,493 KINASE AND HOPE THE NORMAL 2210 01:43:32,493 --> 01:43:34,395 SIGNALLING THROUGH RTKs AND 2211 01:43:34,395 --> 01:43:35,930 NORMAL SIGNALLING FROM THE 2212 01:43:35,930 --> 01:43:38,766 RECEPTOR WILL NOT BE AFFECTED BY 2213 01:43:38,766 --> 01:43:49,043 THESE COMPOUNDS. 2214 01:43:49,543 --> 01:43:53,981 SO, IT'S WHETHER IT'S AN 2215 01:43:53,981 --> 01:43:54,515 EFFECTER. 2216 01:43:54,515 --> 01:43:57,318 WE DID A SEARCH AND SOME PEOPLE 2217 01:43:57,318 --> 01:44:02,757 SHOW RAS PROTEINS ACTIVATING RAF 2218 01:44:02,757 --> 01:44:06,627 AND KINASE AND SOME HAVE THE RAF 2219 01:44:06,627 --> 01:44:07,261 PROTEINS ACTIVATING MULTIPLE 2220 01:44:07,261 --> 01:44:10,364 PATHWAYS AND IF YOU GO TO 2221 01:44:10,364 --> 01:44:14,402 CHATGPT AND ASK WHICH IT 2222 01:44:14,402 --> 01:44:17,805 ACTIVATES AND THE ROLE HAS BEEN 2223 01:44:17,805 --> 01:44:20,308 HARD TO FIGURE OUT BECAUSE FOR 2224 01:44:20,308 --> 01:44:21,943 MULTIPLE FORMS OF RAS AND KINASE 2225 01:44:21,943 --> 01:44:26,147 AND THEY INTERACT IN COMPLICATED 2226 01:44:26,147 --> 01:44:26,347 WAYS. 2227 01:44:26,347 --> 01:44:35,489 I'LL SKIP THE NEXT SLIDE. 2228 01:44:35,489 --> 01:44:39,360 THIS IS A KEY SET OF 2229 01:44:39,360 --> 01:44:40,861 PUBLICATIONS THAT'S THE BASIS OF 2230 01:44:40,861 --> 01:44:42,229 OUR APPROACH. 2231 01:44:42,229 --> 01:44:48,202 TO INTERROGATE THE INTERACTION 2232 01:44:48,202 --> 01:44:50,738 THEY COMBINE ANY RAS PROTEINS. 2233 01:44:50,738 --> 01:44:52,506 AND KNOCKED THE MUTATIONS INTO 2234 01:44:52,506 --> 01:44:53,741 ADULT MICE AND SHOWED THE MICE 2235 01:44:53,741 --> 01:45:00,681 ARE HEALTHY AND SURVIVE OKAY 2236 01:45:00,681 --> 01:45:09,090 DON'T GET HYPOGLYCEMIA AND BUT 2237 01:45:09,090 --> 01:45:12,126 DEFECTIVE IN IT HYPO-GENESIS AND 2238 01:45:12,126 --> 01:45:15,296 YOU CAN EFFECT TUMORIGENESIS 2239 01:45:15,296 --> 01:45:16,464 WITHOUT ANY OBVIOUS SIDE EFFECTS 2240 01:45:16,464 --> 01:45:17,031 ON THE HOST. 2241 01:45:17,031 --> 01:45:25,272 WHAT WE WANT IS A DRUG THAT A 2242 01:45:25,272 --> 01:45:33,614 GROUP SHOWED YEARS AGO. 2243 01:45:33,614 --> 01:45:44,125 SO THIS INTRODUCES A COMPOUND 2244 01:45:55,503 --> 01:45:58,739 AND WE HAVE CREATIVE PARTNERS 2245 01:45:58,739 --> 01:45:59,340 AND COLLABORATORS AT THE 2246 01:45:59,340 --> 01:46:01,842 NATIONAL LAB. 2247 01:46:01,842 --> 01:46:06,547 THE ESSENCE OF THIS COMPOUND IS 2248 01:46:06,547 --> 01:46:07,348 SUMMARIZED IN THE TABLE HERE. 2249 01:46:07,348 --> 01:46:10,751 YOU SEE TARGETED ENGAGEMENT OF 2250 01:46:10,751 --> 01:46:14,755 THE KINASE ALPHA AND THREE NANO 2251 01:46:14,755 --> 01:46:20,528 MOLAR IN CELLS AND BINDS 2252 01:46:20,528 --> 01:46:23,164 SUSTAINED IN THE RAS DOMAIN AND 2253 01:46:23,164 --> 01:46:24,465 PROPERTIES AND SOME I'LL SHOW 2254 01:46:24,465 --> 01:46:24,665 HERE. 2255 01:46:24,665 --> 01:46:28,736 THE WHOLE WORK IS ENABLED BY THE 2256 01:46:28,736 --> 01:46:30,538 RAS PROTEINS IN THE KINASE ALPHA 2257 01:46:30,538 --> 01:46:31,472 FOR THE FIRST TIME AND YOU SEE 2258 01:46:31,472 --> 01:46:34,475 ON THE LEFT IS THE STRUCTURE OF 2259 01:46:34,475 --> 01:46:37,211 K RAS BOUND KINASE AND THE BLUE 2260 01:46:37,211 --> 01:46:40,581 IS THE WILL RAS BINDING DOMAIN 2261 01:46:40,581 --> 01:46:43,250 WHERE THE IT INTERACTS AND THE 2262 01:46:43,250 --> 01:46:45,119 COMPOUND BINDS TO KINASE AND 2263 01:46:45,119 --> 01:46:46,754 PREVENTS RAS PROTEINS BINDING AT 2264 01:46:46,754 --> 01:46:56,931 THAT SITE. 2265 01:47:07,942 --> 01:47:11,178 IT CAN WHACK THE INTERACTION. 2266 01:47:11,178 --> 01:47:14,915 WE CAN PREVENT THE KINASE ALPHA 2267 01:47:14,915 --> 01:47:17,551 BINDING TO PROTEINS SHOWING DOSE 2268 01:47:17,551 --> 01:47:22,156 DEPENDENT CURVE ON THE LEFT. 2269 01:47:22,156 --> 01:47:27,394 PREVENTING BINDING TO THE 6 NANO 2270 01:47:27,394 --> 01:47:28,963 MOLAR IN CELLS AND RECOMBINANT 2271 01:47:28,963 --> 01:47:31,298 PROTEINS AND SEE ON THE LEFT 2272 01:47:31,298 --> 01:47:33,834 THEY BIND BUT THE COMPOUND 2273 01:47:33,834 --> 01:47:35,369 PREVENTS BINDING AND IMPORTANTLY 2274 01:47:35,369 --> 01:47:38,339 THE COMPOUND IN THE BOTTOM PANEL 2275 01:47:38,339 --> 01:47:40,074 DOES NOT AFFECT THE IT KINASE 2276 01:47:40,074 --> 01:47:42,409 ACTIVITY DIRECTLY IN THE TEST 2277 01:47:42,409 --> 01:47:45,679 TUBE WHERE THE DRUG APPROVED 2278 01:47:45,679 --> 01:47:47,481 MUTANT FOR METASTATIC BREAST 2279 01:47:47,481 --> 01:47:53,354 CANCER POTENT. 2280 01:47:53,354 --> 01:47:55,156 -- POTENTLY INHIBITS IT AND 2281 01:47:55,156 --> 01:47:57,591 PREVENTS THE KINASE ALPHA AND 2282 01:47:57,591 --> 01:47:59,193 THAT'S WHERE OUR SELECTIVITY 2283 01:47:59,193 --> 01:48:01,395 COMES FROM AND HOPES WHERE OUR 2284 01:48:01,395 --> 01:48:09,603 SAFETY COMES FROM. 2285 01:48:09,603 --> 01:48:13,140 WE TESTED THIS COMPOUND IN CELLS 2286 01:48:13,140 --> 01:48:16,243 AND FORM THREE BUCKETS, P10 AND 2287 01:48:16,243 --> 01:48:19,280 CELLS DON'T RESPOND VERY WELL. 2288 01:48:19,280 --> 01:48:22,082 THE MUTANT K RAS OR THE KINASE 2289 01:48:22,082 --> 01:48:23,450 ALPHA SHOW GOOD RESPONSES BUT 2290 01:48:23,450 --> 01:48:24,585 NOT COMPLETE. 2291 01:48:24,585 --> 01:48:27,755 AND THE BIG SURPRISE IS THE CELL 2292 01:48:27,755 --> 01:48:29,890 LINE WITH NEW AMPLIFICATION ARE 2293 01:48:29,890 --> 01:48:30,491 EXTREMELY RESPONSIVE TO THIS 2294 01:48:30,491 --> 01:48:32,726 COMPOUND. 2295 01:48:32,726 --> 01:48:36,163 THAT WAS A BIG SURPRISE BECAUSE 2296 01:48:36,163 --> 01:48:37,431 IN LITERATURE THE ACTIVATION OF 2297 01:48:37,431 --> 01:48:39,633 THE KINASE IS RAS INDEPENDENT. 2298 01:48:39,633 --> 01:48:40,201 I'LL GET BACK IT THAT IN A 2299 01:48:40,201 --> 01:48:43,537 MOMENT. 2300 01:48:43,537 --> 01:48:45,239 TOP RIGHT SHOWS TARGETED 2301 01:48:45,239 --> 01:48:46,874 ENGAGEMENT ASSAY. 2302 01:48:46,874 --> 01:48:48,642 IN ALL THE GENOTYPES WE ENGAGE 2303 01:48:48,642 --> 01:48:51,212 THE TARGET EFFICIENTLY AND STILL 2304 01:48:51,212 --> 01:48:53,280 BINDING THE KINASE ALPHA 2305 01:48:53,280 --> 01:48:56,283 COVALENTLY BUT SHUTTING DOWN THE 2306 01:48:56,283 --> 01:48:57,585 INTERACTION DOESN'T HAVE A 2307 01:48:57,585 --> 01:48:59,253 COMPLETE EFFECT ON ALPHA IN 2308 01:48:59,253 --> 01:49:00,554 DIFFERENT CELL LINES BECAUSE 2309 01:49:00,554 --> 01:49:01,422 ALPHA CAN BE ACTIVATED BY 2310 01:49:01,422 --> 01:49:04,058 DIFFERENT PATHWAYS. 2311 01:49:04,058 --> 01:49:06,760 AND THE BOTTOM PANEL SHOW WHOLE 2312 01:49:06,760 --> 01:49:08,996 PANEL CELL LINE WITH MUTATIONS 2313 01:49:08,996 --> 01:49:11,432 ALL RESPOND TO SOME DEGREE BUT 2314 01:49:11,432 --> 01:49:13,300 THE WINNER HERE IS A NEW PANEL 2315 01:49:13,300 --> 01:49:17,671 WE SEE EXTREMELY POTENT EFFECTS 2316 01:49:17,671 --> 01:49:18,872 ON KINASE AND ON GROWTH 3-D AND 2317 01:49:18,872 --> 01:49:26,714 IN VIVO. 2318 01:49:26,714 --> 01:49:29,316 IN THE CASE OF THE K RAS MUTANTS 2319 01:49:29,316 --> 01:49:30,584 NOT INTERROGATED FOR THE FIRST 2320 01:49:30,584 --> 01:49:33,187 TIME EXACTLY WHAT THE ROLE IS OF 2321 01:49:33,187 --> 01:49:37,992 K RAS AND ACTIVATING PF3 KINASE. 2322 01:49:37,992 --> 01:49:40,060 THE LEFT PANEL SHOWS IN THE D12C 2323 01:49:40,060 --> 01:49:50,604 CELL LINE IF YOU TREAT THEM WITH 2324 01:49:52,940 --> 01:49:53,207 AL 2325 01:49:53,207 --> 01:49:54,475 ALPELISIB COMES THROUGH ALPHA 2326 01:49:54,475 --> 01:49:58,746 AND WHAT IS IN GREEN IS SIMILAR 2327 01:49:58,746 --> 01:50:01,248 IN SHUTTING DOWN MOST THE KINASE 2328 01:50:01,248 --> 01:50:03,217 ACTIVITY WE CAN CONCLUDE MOST 2329 01:50:03,217 --> 01:50:05,853 COMES THROUGH RAS PROTEINS IN 2330 01:50:05,853 --> 01:50:07,254 THESE CELLS SAME WITH THE PANEL 2331 01:50:07,254 --> 01:50:09,590 ON THE RIGHT BUT THERE'S STILL 2332 01:50:09,590 --> 01:50:12,126 RESIDUAL ACTIVITY WE THINK COMES 2333 01:50:12,126 --> 01:50:13,560 STRAIGHT FROM THE RECEPTOR 2334 01:50:13,560 --> 01:50:16,430 WITHOUT USE RAS. 2335 01:50:16,430 --> 01:50:16,897 SO THAT'S RELATIVELY 2336 01:50:16,897 --> 01:50:18,532 STRAIGHTFORWARD HELPS UNDERSTAND 2337 01:50:18,532 --> 01:50:21,001 HOW RAS PLAYS A ROLE IN 2338 01:50:21,001 --> 01:50:22,036 REGULATING THE PATHWAY FOR THE 2339 01:50:22,036 --> 01:50:30,044 FIRST TIME IN CELL LINES. 2340 01:50:30,044 --> 01:50:32,846 THIS IS THE BIG SURPRISE IN 2341 01:50:32,846 --> 01:50:34,748 AMPLIFIED CELL LINES MOST THE 2342 01:50:34,748 --> 01:50:36,450 ALPHA ACTIVITY COMES FROM 2343 01:50:36,450 --> 01:50:36,950 SOMEWHERE ELSE. 2344 01:50:36,950 --> 01:50:39,787 SO JUST LOOKING AT THE RIGHT 2345 01:50:39,787 --> 01:50:42,756 PANEL AND WELL KNOWN CELL LINE 2346 01:50:42,756 --> 01:50:49,330 AND TREAT THESE WITH ALPELISIB 2347 01:50:49,330 --> 01:50:52,199 AND IT WORKS AND THE BREAKUP IN 2348 01:50:52,199 --> 01:50:54,802 RED ALSO SHUTS DOWN MOST THE 2349 01:50:54,802 --> 01:50:57,671 KINASE ACTIVITY. 2350 01:50:57,671 --> 01:51:02,509 HOWEVER, THE INHIBITOR WHICH 2351 01:51:02,509 --> 01:51:05,412 INHIBITS HMK AND REM NAS HAS 2352 01:51:05,412 --> 01:51:06,113 LITTLE AFFECT. 2353 01:51:06,113 --> 01:51:08,282 SOME BUT NOT MAJORITY EFFECT. 2354 01:51:08,282 --> 01:51:11,085 SO THERE WAS A LARGE AMOUNT OF 2355 01:51:11,085 --> 01:51:12,820 ACTIVITY WHICH IS NOT ACCOUNTED 2356 01:51:12,820 --> 01:51:14,722 FOR BY ANY OF THE KNOWN RAS 2357 01:51:14,722 --> 01:51:19,493 PROTEINS AND WE EXTENDED THIS 2358 01:51:19,493 --> 01:51:24,298 LIST OF UNKNOWNS WHICH ALL THE 2359 01:51:24,298 --> 01:51:26,800 GENES PUBLISHED ARE EXPECTED TO 2360 01:51:26,800 --> 01:51:28,602 BIND AND ACTIVATE THE KINASE 2361 01:51:28,602 --> 01:51:31,605 ALPHA SO IT'S NONE OF THEM. 2362 01:51:31,605 --> 01:51:34,475 NOW WE BASICALLY DISCOVERED A 2363 01:51:34,475 --> 01:51:37,177 NEW CRITICAL PATHWAY FROM KINASE 2364 01:51:37,177 --> 01:51:39,146 WHICH WE PRESUME INVOLVES A 2365 01:51:39,146 --> 01:51:42,216 NOVEL RAS PROTEIN WE SOMEHOW 2366 01:51:42,216 --> 01:51:45,686 MISSED IN THE PAST AND WHEN WE 2367 01:51:45,686 --> 01:51:47,488 UNDERSTAND COULD BE EXTREMELY 2368 01:51:47,488 --> 01:51:48,756 INTERESTING IN UNDERSTANDING HOW 2369 01:51:48,756 --> 01:51:49,957 TO SHUT DOWN SIGNALLING IN THE 2370 01:51:49,957 --> 01:51:50,491 CELLS. 2371 01:51:50,491 --> 01:51:52,192 THAT'S AN ACADEMIC ISSUE. 2372 01:51:52,192 --> 01:51:55,662 FROM THE PRACTICAL POINT OF VIEW 2373 01:51:55,662 --> 01:51:58,732 THE COMPOUND IS POTENT IN THE 2374 01:51:58,732 --> 01:52:06,673 GENOTYPE. 2375 01:52:06,673 --> 01:52:10,010 THE COMPOUND PLAYS OUT AS WE 2376 01:52:10,010 --> 01:52:13,947 HOPE IS NOT JUST KINASE 2377 01:52:13,947 --> 01:52:18,752 INHIBITOR BUT DOESN'T PROMOTE 2378 01:52:18,752 --> 01:52:24,024 GLYCEMIA AND THE ALPELISIB CAN 2379 01:52:24,024 --> 01:52:33,133 INDUCE HYPOGLYCEMIA AND IF YOU 2380 01:52:33,133 --> 01:52:37,070 GIVE MICE A GLUCOSE CHALLENGE OR 2381 01:52:37,070 --> 01:52:40,207 YOU SEE IN BLUE THE TREATED MICE 2382 01:52:40,207 --> 01:52:42,743 AND THE BLACK YOU SEE NO 2383 01:52:42,743 --> 01:52:45,579 ACCUMULATION OF GLUCOSE BUT THE 2384 01:52:45,579 --> 01:52:46,814 GREEN LINE SHOWS TREATMENT AND 2385 01:52:46,814 --> 01:52:49,016 YOU CAN SEE THE SAME ON THE 2386 01:52:49,016 --> 01:52:53,620 RIGHT PANEL WITH INSULIN WHICH 2387 01:52:53,620 --> 01:52:55,556 ACCUMULATES AS A RESULT OF 2388 01:52:55,556 --> 01:52:57,324 HYPERGLYCEMIA AND FAILURE TO 2389 01:52:57,324 --> 01:53:02,863 CONTROL THE SIGNALLING PATHWAY. 2390 01:53:02,863 --> 01:53:04,865 SO SHUTTING DOWN THE PATHWAY AND 2391 01:53:04,865 --> 01:53:09,303 ON THE LEFT PANEL WE DON'T 2392 01:53:09,303 --> 01:53:10,704 PROMOTE HYPERGLYCEMIA. 2393 01:53:10,704 --> 01:53:12,039 WE THINK IT WILL MAKE THE 2394 01:53:12,039 --> 01:53:13,607 COMPOUNDS MORE EASY TO USE IN 2395 01:53:13,607 --> 01:53:16,877 THE CLINIC AND KEEPING THE 2396 01:53:16,877 --> 01:53:19,346 EFFICACY OR I AM IMPROVING IT 2397 01:53:19,346 --> 01:53:22,749 BECAUSE WE CAN DOSE HIGHER 2398 01:53:22,749 --> 01:53:26,620 WITHOUT SIDE EFFECTS. 2399 01:53:26,620 --> 01:53:29,690 IT OPENS UP THE POSSIBILITY OF 2400 01:53:29,690 --> 01:53:30,624 COMBINATION THERAPY. 2401 01:53:30,624 --> 01:53:34,361 SO ONE OF OUR FIRST COMBINATIONS 2402 01:53:34,361 --> 01:53:36,730 WE'LL TEST IS WITH THE ACTIVE 2403 01:53:36,730 --> 01:53:37,030 COMPOUND. 2404 01:53:37,030 --> 01:53:40,567 SO ON THE LEFT PANEL WE SHOWED 2405 01:53:40,567 --> 01:53:42,736 THE EFFECTS OF B12C ACTIVE 2406 01:53:42,736 --> 01:53:43,670 COMPOUND IN GREEN. 2407 01:53:43,670 --> 01:53:46,039 PRETTY EFFECTIVE IN THE CELL 2408 01:53:46,039 --> 01:53:47,941 LINE MODEL AND THE COMBINATION 2409 01:53:47,941 --> 01:53:52,045 IN RED MUCH MORE EFFECTIVE. 2410 01:53:52,045 --> 01:53:52,746 MORE IMPORTANTLY IN LUNG CANCER 2411 01:53:52,746 --> 01:53:56,850 CELL LINES AND MUTATIONS, THESE 2412 01:53:56,850 --> 01:53:58,819 CELLS ARE REFRACTORY IN THE 2413 01:53:58,819 --> 01:54:02,523 CLINIC TO G12C INHIBITORS. 2414 01:54:02,523 --> 01:54:04,124 WE SEE HERE IN COMBINATION WITH 2415 01:54:04,124 --> 01:54:07,928 OUR INHIBITOR ANTITUMOR 2416 01:54:07,928 --> 01:54:09,429 RESPONSES IN THE SITUATION. 2417 01:54:09,429 --> 01:54:11,832 AND THE RIGHT HAND PANEL IS 2418 01:54:11,832 --> 01:54:15,068 ANOTHER NOTORIOUSLY RESISTANT 2419 01:54:15,068 --> 01:54:16,336 CELL LINE AND GET RESPONSES IN 2420 01:54:16,336 --> 01:54:18,338 COMBINATION WITH INHIBITORS. 2421 01:54:18,338 --> 01:54:20,274 THE COMBINATION IS ONE OF THE 2422 01:54:20,274 --> 01:54:22,743 FIRST THINGS WELL TEST TO 2423 01:54:22,743 --> 01:54:24,478 ENHANCE ACTIVITY OF G12C ON AND 2424 01:54:24,478 --> 01:54:25,479 OFF COMPOUNDS IN THE CLINICAL 2425 01:54:25,479 --> 01:54:34,054 SETTINGS. 2426 01:54:34,054 --> 01:54:35,756 WE CAN GO BEYOND THAT AND IF YOU 2427 01:54:35,756 --> 01:54:37,357 FOLLOW DRUG RESISTANCE FOR MANY 2428 01:54:37,357 --> 01:54:41,962 YEARS OR FULLY AWARE OF THE FACT 2429 01:54:41,962 --> 01:54:44,064 THE KINASE ACTIVITY IS OFTEN 2430 01:54:44,064 --> 01:54:45,265 ASSOCIATED WITH DRUG RESISTANCE 2431 01:54:45,265 --> 01:54:49,336 IN MANY CONTEXTS INCLUDING CHEMO 2432 01:54:49,336 --> 01:54:50,537 AND TARGET AND OTHER THERAPIES 2433 01:54:50,537 --> 01:54:52,205 AND MODALITIES. 2434 01:54:52,205 --> 01:54:54,741 IN THIS CASE WE DON'T UNDERSTAND 2435 01:54:54,741 --> 01:54:58,111 HOW THE KINASE ACTIVATION CO 2436 01:54:58,111 --> 01:55:00,547 CONFERS THESE RESISTANT EFFECTS 2437 01:55:00,547 --> 01:55:02,349 BUT IT'S A PROBLEM. 2438 01:55:02,349 --> 01:55:08,388 AND LIKELY THE ACTIVITY HELPS 2439 01:55:08,388 --> 01:55:11,825 DIVIDE THE AGENTS AND IN 2440 01:55:11,825 --> 01:55:14,194 COMBINATION WITH THREE DIFFERENT 2441 01:55:14,194 --> 01:55:20,467 DRUGS THAT ARE USED ROUTINELY IN 2442 01:55:20,467 --> 01:55:22,736 BREAST CANCER. 2443 01:55:22,736 --> 01:55:26,673 AND YOU CAN SEE THESE DOSES HAVE 2444 01:55:26,673 --> 01:55:29,676 BEEN ADJUSTED FOR PARTIAL EFFECT 2445 01:55:29,676 --> 01:55:32,980 IN BLUE AND BREAK ALONE IS IN 2446 01:55:32,980 --> 01:55:35,983 GREEN AND THE COMBINATION OF THE 2447 01:55:35,983 --> 01:55:38,085 BREAKER PLUS THE TARGETED 2448 01:55:38,085 --> 01:55:39,686 THERAPIES GIVES MORE DRAMATIC 2449 01:55:39,686 --> 01:55:39,953 RESPONSES. 2450 01:55:39,953 --> 01:55:41,521 AND WE SEE THIS ALSO IN 2451 01:55:41,521 --> 01:55:43,223 COMBINATION WITH OTHER 2452 01:55:43,223 --> 01:55:46,126 CHEMOTHERAPY AN OTHER RESPONSES. 2453 01:55:46,126 --> 01:55:49,363 SO IF WE ARE CORRECT AND CAN USE 2454 01:55:49,363 --> 01:55:55,168 THE DRUG WITHOUT PROVOKING HY 2455 01:55:55,168 --> 01:55:58,205 HYPERGLYCEMIA OR OTHER EFFECTS 2456 01:55:58,205 --> 01:56:00,974 WE THINK IT WILL HAVE OTHER 2457 01:56:00,974 --> 01:56:04,945 ROLES WHERE PF3 KINASE 2458 01:56:04,945 --> 01:56:05,946 ACTIVATION IS A MAJOR PROBLEM 2459 01:56:05,946 --> 01:56:06,947 AND CAUSE OF RESISTANCE IN 2460 01:56:06,947 --> 01:56:10,751 MR. CASES. 2461 01:56:10,751 --> 01:56:19,426 -- MANY CASES. 2462 01:56:19,426 --> 01:56:22,462 TO SUMMARIZE IN THE WORLD WE'RE 2463 01:56:22,462 --> 01:56:25,465 TARGETING ONCOGENIC RAS AND THE 2464 01:56:25,465 --> 01:56:26,800 MYSTERY RAS PROTEIN HERE SHOWN 2465 01:56:26,800 --> 01:56:30,103 IN MAGENTA AND OTHERS INVOLVED 2466 01:56:30,103 --> 01:56:33,907 IN PATHOGENIC SITUATION USING A 2467 01:56:33,907 --> 01:56:35,275 COMPOUND WHERE THE SITUATIONS 2468 01:56:35,275 --> 01:56:40,147 ARE NOT NORMAL SIGNALLING. 2469 01:56:40,147 --> 01:56:45,318 AND THE LAST SLIDE GIVES CREDIT 2470 01:56:45,318 --> 01:56:49,389 TO THE TEAM LED BY FREDERICK 2471 01:56:49,389 --> 01:56:50,891 NATIONAL LAB AND A TIGHT 2472 01:56:50,891 --> 01:56:55,662 COLLABORATION AND BIG TEAM 2473 01:56:55,662 --> 01:56:58,732 EFFORT WITH OUR COLLEAGUES 2474 01:56:58,732 --> 01:57:01,368 DEVELOPING OTHER DRUG AND AN 2475 01:57:01,368 --> 01:57:06,139 INHIBITOR THAT IS NOW APPROVED 2476 01:57:06,139 --> 01:57:10,744 AND THE NATIONAL LAB AND I WANT 2477 01:57:10,744 --> 01:57:13,747 TO ACKNOWLEDGE DWIGHT FOR HIS 2478 01:57:13,747 --> 01:57:15,582 WISDOM AND GUIDANCE AT FREDERICK 2479 01:57:15,582 --> 01:57:18,752 NATIONAL LABS AND THANK YOU ALL 2480 01:57:18,752 --> 01:57:19,186 FOR YOUR ATTENTION. 2481 01:57:19,186 --> 01:57:29,362 THANK YOU. 2482 01:57:37,504 --> 01:57:38,705 >> THANK YOU, GREAT REPORT. 2483 01:57:38,705 --> 01:57:39,840 ARE THERE QUESTIONS. 2484 01:57:39,840 --> 01:57:40,774 EARL. 2485 01:57:40,774 --> 01:57:42,409 >> GREAT PRESENTATIONS. 2486 01:57:42,409 --> 01:57:44,177 THANK YOU FOR SUCH NICE WORK AS 2487 01:57:44,177 --> 01:57:44,711 ALWAYS. 2488 01:57:44,711 --> 01:57:46,847 I HAVE TWO QUESTIONS. 2489 01:57:46,847 --> 01:57:51,451 ONE, WHAT IS KNOWN ABOUT THE 2490 01:57:51,451 --> 01:57:53,353 MUTATIONS THE OTHER RAS FAMILY 2491 01:57:53,353 --> 01:57:53,754 MEMBERS? 2492 01:57:53,754 --> 01:57:56,156 ARE THEY CONSERVED IN THE SAME 2493 01:57:56,156 --> 01:57:59,960 LOCATION AS THE MUTATION IS AND 2494 01:57:59,960 --> 01:58:02,362 IS ANYTHING BEING DONE TO TARGET 2495 01:58:02,362 --> 01:58:06,466 THOSE AS WELL? 2496 01:58:06,466 --> 01:58:08,401 AND THE SECOND QUESTION IS DO 2497 01:58:08,401 --> 01:58:10,670 YOU HAVE ANY PROGRESS ON WHAT'S 2498 01:58:10,670 --> 01:58:12,272 BEEN DONE IN TERMS OF GETTING 2499 01:58:12,272 --> 01:58:12,906 THE INFORMATION OUT TO THE LAY 2500 01:58:12,906 --> 01:58:23,049 PUBLIC? 2501 01:58:23,750 --> 01:58:30,724 >> FIRST, WE HAVE A BIG EFFORT 2502 01:58:30,724 --> 01:58:37,030 TARGETING K RAS AND PRIMARILY 2503 01:58:37,030 --> 01:58:38,231 PANCREATIC CANCER BECAUSE WE'RE 2504 01:58:38,231 --> 01:58:42,602 TRYING TO MAKE AN IMPACT IN D12B 2505 01:58:42,602 --> 01:58:44,704 AND D12D. 2506 01:58:44,704 --> 01:58:49,109 THE NEXT COMPOUND HITS THIS 2507 01:58:49,109 --> 01:58:50,443 ALLELES IN THE GTP BOUND STATE 2508 01:58:50,443 --> 01:58:55,081 USING THE SAME MECHANISM AS THE 2509 01:58:55,081 --> 01:58:56,483 G12C. 2510 01:58:56,483 --> 01:58:57,951 WE HAVEN'T FILED THE IND YET BUT 2511 01:58:57,951 --> 01:58:59,753 EXPECT TO SOON AND IF THAT ALL 2512 01:58:59,753 --> 01:59:01,054 CLEARS THEY SHOULD BE IN THE 2513 01:59:01,054 --> 01:59:04,057 CLINIC NEXT YEAR. 2514 01:59:04,057 --> 01:59:06,660 THEY SHOULD TAKE CARE OF SOME OF 2515 01:59:06,660 --> 01:59:08,995 THE OTHER ALLELES THE MORE 2516 01:59:08,995 --> 01:59:10,363 COMMON ONES SO YES THEY'RE 2517 01:59:10,363 --> 01:59:11,131 COMING ALONG. 2518 01:59:11,131 --> 01:59:13,433 AS FOR DISSEMINATION TO THE LAY 2519 01:59:13,433 --> 01:59:17,604 PUBLIC, RIGHT NOW ALL I CAN SAY 2520 01:59:17,604 --> 01:59:20,440 IS WE HAVE SEVERAL MAJOR 2521 01:59:20,440 --> 01:59:21,942 PUBLICATIONS UNDER REVIEW AND 2522 01:59:21,942 --> 01:59:25,245 JOURNALS COMING OUT HOPEFULLY IN 2523 01:59:25,245 --> 01:59:27,380 THE NEAR FUTURE AND THAT IS GOLD 2524 01:59:27,380 --> 01:59:29,115 STANDARD FOR GETTING THE WORD 2525 01:59:29,115 --> 01:59:29,983 OUT TO THE SCIENTIFIC COMMUNITY 2526 01:59:29,983 --> 01:59:33,186 AND AS FOR THE LAY PUBLIC I 2527 01:59:33,186 --> 01:59:34,821 THINK I'LL DEFER TO MY 2528 01:59:34,821 --> 01:59:36,223 COLLEAGUES AT THE NCI OR 2529 01:59:36,223 --> 01:59:43,430 FREDERICK FOR THAT COMMENT. 2530 01:59:43,430 --> 01:59:45,899 >> YES, MATT. 2531 01:59:45,899 --> 01:59:50,136 >> THAT WAS AMAZING WORK AS 2532 01:59:50,136 --> 01:59:50,403 ALWAYS. 2533 01:59:50,403 --> 01:59:52,272 I HAVE IN THINKING ABOUT THE 2534 01:59:52,272 --> 01:59:56,509 FINDING WITH THE HER 2 AND 2535 01:59:56,509 --> 01:59:58,845 BREAKER COMPOUND IS INTRIGUING 2536 01:59:58,845 --> 02:00:00,046 AND SURPRISING AND MAKES ME 2537 02:00:00,046 --> 02:00:02,983 WONDER IF YOU LOOKED AT THIS IN 2538 02:00:02,983 --> 02:00:05,352 THE SETTING OF CELLS RESISTANT 2539 02:00:05,352 --> 02:00:11,491 TO STRAIGHT UP RAS INHIBITORS 2540 02:00:11,491 --> 02:00:12,959 THE REASON I'M ASKING IS BECAUSE 2541 02:00:12,959 --> 02:00:14,628 SOMETHING IS ACTIVATING IN THE 2542 02:00:14,628 --> 02:00:16,296 HER 2 POSITIVE SETTING AND THE 2543 02:00:16,296 --> 02:00:18,031 DATA IS PROBABLY CLEAR IT'S 2544 02:00:18,031 --> 02:00:20,367 PROBABLY NOT HER 2 SIGNALLING. 2545 02:00:20,367 --> 02:00:21,334 IT'S INTERESTING YOUR 2546 02:00:21,334 --> 02:00:22,736 POSTULATING IT'S GOING THROUGH 2547 02:00:22,736 --> 02:00:25,939 ANOTHER RAS OR G PROTEIN BUT ONE 2548 02:00:25,939 --> 02:00:28,441 MIGHT IMAGINE THE SAME PATHWAY 2549 02:00:28,441 --> 02:00:33,346 COULD BE ACTIVE AS A RESISTANT 2550 02:00:33,346 --> 02:00:35,615 MECHANISM TO TRADITIONAL 2551 02:00:35,615 --> 02:00:37,484 INHIBITERS BECAUSE THOSE AREN'T 2552 02:00:37,484 --> 02:00:39,686 TARGETING THAT PATHWAY AND YOU 2553 02:00:39,686 --> 02:00:43,957 KNOW ACTIVATING GR2 KINASE CAN 2554 02:00:43,957 --> 02:00:48,361 CONFER SOME KIND OF RESISTANCE. 2555 02:00:48,361 --> 02:00:52,432 FROM A PRACTICAL STANDPOINT IT 2556 02:00:52,432 --> 02:00:54,501 MAYBE THE COMPOUND WILL BE GOOD 2557 02:00:54,501 --> 02:00:55,769 IN THE RAS RESISTANT SETTING FOR 2558 02:00:55,769 --> 02:00:57,170 THOSE REASON IF THAT MAKES 2559 02:00:57,170 --> 02:00:57,370 SENSE. 2560 02:00:57,370 --> 02:01:07,747 >> TOTAL SENSE, YEAH. 2561 02:01:13,486 --> 02:01:14,955 >> GREAT POINT. 2562 02:01:14,955 --> 02:01:18,725 WE DON'T UNDERSTAND AND WE 2563 02:01:18,725 --> 02:01:23,964 INCLUDE HE THE COMBINATION DATA 2564 02:01:23,964 --> 02:01:25,632 WE DON'T UNDERSTAND AND HOPE IT 2565 02:01:25,632 --> 02:01:35,675 CAN BE PICKED UP ON. 2566 02:01:35,675 --> 02:01:38,244 AND THAT OPERATES MORE CASUALLY. 2567 02:01:38,244 --> 02:01:41,381 >> IT COULD BE AN OPPORTUNITY TO 2568 02:01:41,381 --> 02:01:42,749 TRIANGULATE SOME DIFFERENT 2569 02:01:42,749 --> 02:01:44,684 SETTINGS AND MAYBE GET A BETTER 2570 02:01:44,684 --> 02:01:50,190 SENSE OF WHAT THE MYSTERY TARGET 2571 02:01:50,190 --> 02:01:53,193 IS OF THE BREAKER COMPOUND IN 2572 02:01:53,193 --> 02:01:54,461 THE SETTING WHERE IT'S NOT RAS 2573 02:01:54,461 --> 02:01:56,696 BECAUSE KNOWING THAT MAY OPEN UP 2574 02:01:56,696 --> 02:01:59,432 A WHOLE NEW RANGE OF THERAPEUTIC 2575 02:01:59,432 --> 02:01:59,966 POSSIBILITIES. 2576 02:01:59,966 --> 02:02:01,801 >> GREAT POINT, YEAH. 2577 02:02:01,801 --> 02:02:04,671 NOW WE HAVE THE COMPOUNDS THAT 2578 02:02:04,671 --> 02:02:07,007 INHIBITS THE RAS PROTEINS WE CAN 2579 02:02:07,007 --> 02:02:09,175 ELIMINATE THEM MORE EASILY THAN 2580 02:02:09,175 --> 02:02:11,544 DOING KNOCK DOWNS EVEN A YEAR 2581 02:02:11,544 --> 02:02:11,745 AGO. 2582 02:02:11,745 --> 02:02:14,047 I THINK THE TOOLS ARE BETTER FOR 2583 02:02:14,047 --> 02:02:14,748 INTERROGATING THAT. 2584 02:02:14,748 --> 02:02:23,456 THANK YOU. 2585 02:02:23,456 --> 02:02:25,091 >> THAT'S A COMMENT, QUESTION, 2586 02:02:25,091 --> 02:02:26,192 EXCITING WORK. 2587 02:02:26,192 --> 02:02:28,728 WHAT IS THE PLAN FOR THE 2588 02:02:28,728 --> 02:02:30,730 CLINICAL EVALUATION MUCH THE 2589 02:02:30,730 --> 02:02:34,734 BREAKER AS I SOLE AGENT OR IN 2590 02:02:34,734 --> 02:02:44,944 COMBINATION? 2591 02:02:52,752 --> 02:02:53,086 S 2592 02:02:53,086 --> 02:02:55,321 >> WITH THINK IT THE SHOW IN 2593 02:02:55,321 --> 02:02:56,890 COLORECTAL AND SMALL CELL LUNG 2594 02:02:56,890 --> 02:03:00,326 AND IF THE COMPOUND IS SAFE AND 2595 02:03:00,326 --> 02:03:02,429 THERE'S MONOTHERAPY INDICATIONS 2596 02:03:02,429 --> 02:03:05,865 WE'LL SWITCH TO THE OBVIOUS ONES 2597 02:03:05,865 --> 02:03:06,666 WE JUST REFERRED TO. 2598 02:03:06,666 --> 02:03:07,467 WE HAVE A PLAN FOR TACKLING 2599 02:03:07,467 --> 02:03:16,242 THOSE. 2600 02:03:16,242 --> 02:03:18,378 BREAST CANCER IS ON OUR RADAR 2601 02:03:18,378 --> 02:03:22,582 SCREEN AND WE SEE GREAT ENERGY 2602 02:03:22,582 --> 02:03:25,718 WITH CDK4 INHIBITERS AND IT'S AN 2603 02:03:25,718 --> 02:03:26,753 OBVIOUS PLACE TO GO. 2604 02:03:26,753 --> 02:03:27,887 >> THANKS, FRANK. 2605 02:03:27,887 --> 02:03:30,723 I THINK WE NEED TO MOVE ON. 2606 02:03:30,723 --> 02:03:31,057 APPRECIATE IT. 2607 02:03:31,057 --> 02:03:33,793 THANK YOU, McCORMICK. 2608 02:03:33,793 --> 02:03:34,928 OUR NEXT PRESENTATION IS BY 2609 02:03:34,928 --> 02:03:37,397 DR. SINGER AND PINTO TALKING 2610 02:03:37,397 --> 02:03:40,700 ABOUT THE SEROLOGICAL SCIENCES 2611 02:03:40,700 --> 02:03:47,073 NETWORK SER NET IN RESPONSE TO 2612 02:03:47,073 --> 02:03:47,340 COVID-19. 2613 02:03:47,340 --> 02:03:55,715 MANY KNOW THESE WERE SHINING 2614 02:03:55,715 --> 02:03:57,884 MOMENTS FOR FNLAC WHERE THEY 2615 02:03:57,884 --> 02:03:58,485 CONTRIBUTED SIGNIFICANTLY SO, 2616 02:03:58,485 --> 02:04:08,628 PLEASE. 2617 02:04:12,932 --> 02:04:14,634 >> DR. SINGER WAS HAVING WEBEX 2618 02:04:14,634 --> 02:04:17,604 ISSUES AND WAS GOING TO CALL IN 2619 02:04:17,604 --> 02:04:18,905 IF SHE WASN'T ABLE TO AND SHE 2620 02:04:18,905 --> 02:04:19,472 MAY BE MUTED. 2621 02:04:19,472 --> 02:04:29,616 >> OKAY. 2622 02:04:39,259 --> 02:04:49,602 >> DR. SINGER IS MUTED. 2623 02:04:58,578 --> 02:05:01,114 CAN YOU UNMUTE HER? 2624 02:05:01,114 --> 02:05:05,718 >> I'M CHECKING. 2625 02:05:05,718 --> 02:05:06,686 A/V SUPPORT CAN WE UNMUTE? 2626 02:05:06,686 --> 02:05:08,755 >> I DON'T THINK WE CAN. 2627 02:05:08,755 --> 02:05:10,723 >> YOU'RE GOOD. 2628 02:05:10,723 --> 02:05:11,925 THANK YOU. 2629 02:05:11,925 --> 02:05:12,192 OKAY. 2630 02:05:12,192 --> 02:05:12,392 SORRY. 2631 02:05:12,392 --> 02:05:13,059 >> NO PROBLEM. 2632 02:05:13,059 --> 02:05:16,796 >> WELL, ANYHOW, THANK YOU FOR 2633 02:05:16,796 --> 02:05:19,465 LETTING ME GIVE YOU A VERY BRIEF 2634 02:05:19,465 --> 02:05:21,634 UPDATE ON THE SEROLOGICAL 2635 02:05:21,634 --> 02:05:24,604 SCIENCES NETWORK OR SERONET 2636 02:05:24,604 --> 02:05:28,107 WHICH WAS ESTABLISHED BACK IN 2637 02:05:28,107 --> 02:05:29,609 2020 IN RESPONSE TO 2638 02:05:29,609 --> 02:05:30,944 CONGRESSIONAL APPROPRIATION OF 2639 02:05:30,944 --> 02:05:34,647 ABOUT $300 MILLION TO NCI TO 2640 02:05:34,647 --> 02:05:38,651 PROVIDE BOTH SEROLOGICAL SEFT OF 2641 02:05:38,651 --> 02:05:39,552 TESTING AND SUPPORT SUPPORT 2642 02:05:39,552 --> 02:05:43,456 RESEARCH ON THE OVER ALL 2643 02:05:43,456 --> 02:05:53,833 RESPONSE TO SARS COV2. 2644 02:05:58,605 --> 02:05:59,505 SERONET WAS ESTABLISHED AFTER 2645 02:05:59,505 --> 02:06:02,742 CONGRESSIONAL APPROPRIATION WITH 2646 02:06:02,742 --> 02:06:10,750 THE GOALS OF DEVELOPING AND 2647 02:06:10,750 --> 02:06:21,261 DEPLOYING BROADLY SEROLOGICAL 2648 02:06:23,429 --> 02:06:23,763 SEA 2649 02:06:23,763 --> 02:06:25,798 SARS COV2 AND DETERMINE 2650 02:06:25,798 --> 02:06:26,766 SEROLOGICAL CORRELATES AND 2651 02:06:26,766 --> 02:06:30,737 BARRIERS TO VANING. 2652 02:06:30,737 --> 02:06:33,006 -- VACCINATION. 2653 02:06:33,006 --> 02:06:37,477 A NETWORK CONSISTS OF A TOTAL OF 2654 02:06:37,477 --> 02:06:39,846 FOUR COMPONENTS. 2655 02:06:39,846 --> 02:06:44,384 FOUR, 21 RESEARCH GRANTS, 13 2656 02:06:44,384 --> 02:06:47,520 WERE UL 1s AND THEY WERE CHARGED 2657 02:06:47,520 --> 02:06:49,889 WITH THE BASIC RESEARCH OF 2658 02:06:49,889 --> 02:06:53,626 CHARACTERIZING THE IMMUNE 2659 02:06:53,626 --> 02:06:58,731 RESPONSE TO SARS COV2 AS WELL AS 2660 02:06:58,731 --> 02:07:02,302 IS SEROLOGICAL RESEARCH AND HAD 2661 02:07:02,302 --> 02:07:08,041 CAPACITY BUILDING CENTERS TO 2662 02:07:08,041 --> 02:07:10,009 GENERATOR MAKE AVAILABLE IS 2663 02:07:10,009 --> 02:07:14,347 SEROLOGICAL TESTING NATIONALLY 2664 02:07:14,347 --> 02:07:18,418 AND USE BIO SPECIMENS AND FOR 2665 02:07:18,418 --> 02:07:19,218 ESTABLISHING STANDARDS AND THEY 2666 02:07:19,218 --> 02:07:22,855 WERE ALSO CHARGED WITH 2667 02:07:22,855 --> 02:07:26,526 CONDUCTING SURVEILLANCE STUDIES. 2668 02:07:26,526 --> 02:07:29,829 THE THIRD COMPONENT WAS ALSO 2669 02:07:29,829 --> 02:07:31,297 SEROLOGY LAB THAT WAS CHARGED 2670 02:07:31,297 --> 02:07:35,802 WITH HELPING THE FDA TO ASSESS 2671 02:07:35,802 --> 02:07:37,337 COMMERCIAL SEROLOGY DEVICES AND 2672 02:07:37,337 --> 02:07:38,738 TO DEVELOP SEROLOGY ASSAYS AND 2673 02:07:38,738 --> 02:07:40,540 STANDARDS. 2674 02:07:40,540 --> 02:07:43,910 AND THEN THE LAST PIECE WAS A 2675 02:07:43,910 --> 02:07:45,678 NETWORK COORDINATING CENTER TO 2676 02:07:45,678 --> 02:07:51,517 TRY TO MANAGE AND COORDINATE ALL 2677 02:07:51,517 --> 02:07:58,725 THE ACTIVITIES OF SERONET. 2678 02:07:58,725 --> 02:08:00,159 SO, ONE NOTEWORTHY ASPECT THAT 2679 02:08:00,159 --> 02:08:03,863 SETS IT ASIDE FROM OTHER EFFORTS 2680 02:08:03,863 --> 02:08:06,532 TO STUDY SARS COV2 INFECTION WAS 2681 02:08:06,532 --> 02:08:10,737 ITS FOCUS ON SPECIAL POPULATIONS 2682 02:08:10,737 --> 02:08:14,741 INCLUDING CANCER PATIENTS AND 2683 02:08:14,741 --> 02:08:16,309 IMMUNOCOMPROMISED PATIENTS, 2684 02:08:16,309 --> 02:08:18,311 PATIENTS WITH A VARIETY OF 2685 02:08:18,311 --> 02:08:18,911 IMMUNE MEDIATED INFLAMMATORY 2686 02:08:18,911 --> 02:08:23,850 DISEASES. 2687 02:08:23,850 --> 02:08:26,452 AS WE STOOD SERONET UP WE 2688 02:08:26,452 --> 02:08:27,787 ADOPTED A NUMBER OF PRINCIPLES 2689 02:08:27,787 --> 02:08:31,524 TO WORK ACROSS THE NETWORK. 2690 02:08:31,524 --> 02:08:34,494 ONE WAS IN ORDER TO MAKE AS MUCH 2691 02:08:34,494 --> 02:08:37,764 AS INFORMATION AVAILABLE AS 2692 02:08:37,764 --> 02:08:38,965 QUICKLY AS POSSIBLE ALL SERONET 2693 02:08:38,965 --> 02:08:41,701 PUBLICATIONS HAD TO APPEAR IN AN 2694 02:08:41,701 --> 02:08:43,169 OPEN ACCESS FORMAT. 2695 02:08:43,169 --> 02:08:44,871 ALL THE DATA UNDERLYING THE 2696 02:08:44,871 --> 02:08:45,872 RESEARCH HAS TO BE SHARED 2697 02:08:45,872 --> 02:08:49,409 IMMEDIATELY FOR PUBLICATION AND 2698 02:08:49,409 --> 02:08:53,713 FINALLY WITHIN SERONET A NETWORK 2699 02:08:53,713 --> 02:08:55,548 WIDE AGREEMENT TO SHARE 2700 02:08:55,548 --> 02:08:58,751 INFORMATION PREPUBLICATION AND 2701 02:08:58,751 --> 02:09:01,988 COLLABORATE EXTENSIVELY. 2702 02:09:01,988 --> 02:09:03,589 BECAUSE SERONET WAS STOOD UP IN 2703 02:09:03,589 --> 02:09:06,726 2020 IN THE HEIGHT OF THE 2704 02:09:06,726 --> 02:09:08,861 PANDEMIC, WE ANTICIPATED THE 2705 02:09:08,861 --> 02:09:10,363 PANDEMIC WOULD CHANGE OVER TIME 2706 02:09:10,363 --> 02:09:12,799 AND WE WOULD WANT TO RE-ASSESS 2707 02:09:12,799 --> 02:09:17,370 THE PROGRESS OF THE GRANTS AND 2708 02:09:17,370 --> 02:09:19,605 THE CDCs CENTERS AFTER A PERIOD 2709 02:09:19,605 --> 02:09:22,341 OF TIME TO MAKE SURE THEY WERE 2710 02:09:22,341 --> 02:09:26,345 FOCUSSING ON THE RELEVANT 2711 02:09:26,345 --> 02:09:27,346 PROBLEMS THAT WE HEARD AFTER TWO 2712 02:09:27,346 --> 02:09:32,185 YEARS OF FUNDING. 2713 02:09:32,185 --> 02:09:33,586 SO BUILT INTO OUR PROGRAM WAS 2714 02:09:33,586 --> 02:09:35,321 THE RE-ASSESSMENT AFTER TWO 2715 02:09:35,321 --> 02:09:36,622 YEARS OF THE PROGRAM 2716 02:09:36,622 --> 02:09:38,658 SPECIFICALLY OF THE CAPACITY 2717 02:09:38,658 --> 02:09:39,225 BUILDING CENTERS AND OF THE 2718 02:09:39,225 --> 02:09:40,960 GRANTS. 2719 02:09:40,960 --> 02:09:44,897 THE REVIEW WAS CONDUCTED BY A 2720 02:09:44,897 --> 02:09:47,133 PANEL OF EXPERTS AND INTERNAL 2721 02:09:47,133 --> 02:09:50,369 PANEL OF EXPERTS FROM BOTH NCI 2722 02:09:50,369 --> 02:09:52,405 AND THE INSTITUTE, SCIENTISTS 2723 02:09:52,405 --> 02:09:54,740 WHO WERE EXPERT BUT NOT DIRECTLY 2724 02:09:54,740 --> 02:10:05,184 INVOLVED WITH THE PROGRAM. 2725 02:10:08,721 --> 02:10:14,660 SO THE CAPACITY BUILDING CENTER 2726 02:10:14,660 --> 02:10:16,028 ASSESSMENT WAS BASED ON 2727 02:10:16,028 --> 02:10:19,532 SEROLOGICAL TESTING WAS NOT 2728 02:10:19,532 --> 02:10:20,166 CONSIDERED A PRIORITY AND IN 2729 02:10:20,166 --> 02:10:21,501 HIGH DEMAND AT THE TIME. 2730 02:10:21,501 --> 02:10:24,904 IT WAS ASSESSED THE CDC'S 2731 02:10:24,904 --> 02:10:26,539 CONDUCTED IMPORTANT BUT PERHAPS 2732 02:10:26,539 --> 02:10:28,941 NOT UNIQUE RESEARCH AND FINALLY 2733 02:10:28,941 --> 02:10:33,079 THE BIO SPECIMENS BEING 2734 02:10:33,079 --> 02:10:34,747 COLLECTED HAD PROVIDED THE TOTAL 2735 02:10:34,747 --> 02:10:36,415 NUMBER OF BIO SPECIMENS THAT 2736 02:10:36,415 --> 02:10:38,718 WERE NEEDED FOR THE SEROLOGY LAB 2737 02:10:38,718 --> 02:10:42,421 AND WE FOUND THERE WAS A LIMITED 2738 02:10:42,421 --> 02:10:45,591 INTEREST IN SERONET 2739 02:10:45,591 --> 02:10:46,158 INVESTIGATORS IN FURTHER 2740 02:10:46,158 --> 02:10:49,061 COLLECTION OF BIO SPECIMENS. 2741 02:10:49,061 --> 02:10:50,396 SO THE RECOMMENDATION FROM THE 2742 02:10:50,396 --> 02:10:54,734 REVIEW PANEL WAS WE MAINTAIN ONE 2743 02:10:54,734 --> 02:10:57,203 OF THE CDCs TO BE POISED TO 2744 02:10:57,203 --> 02:11:00,172 RESPOND THERE WAS A RESURGENCE 2745 02:11:00,172 --> 02:11:02,408 IN THE PANDEMIC AND ALSO TO 2746 02:11:02,408 --> 02:11:03,676 CONTINUE SOME OF THE RESEARCH 2747 02:11:03,676 --> 02:11:06,746 EFFORTS AND THE LONGITUDINAL 2748 02:11:06,746 --> 02:11:09,715 COHORTS. 2749 02:11:09,715 --> 02:11:15,688 OF THE 21 GRANTS, ALL BUT ONE 2750 02:11:15,688 --> 02:11:17,290 WERE APPROVED FOR CONTINUATION. 2751 02:11:17,290 --> 02:11:18,524 ONE ON THE EXTENSION. 2752 02:11:18,524 --> 02:11:21,193 OF THE GRANTS THAT WERE APPROVED 2753 02:11:21,193 --> 02:11:23,629 FOR CONTINUATION, WE ALLOWED 2754 02:11:23,629 --> 02:11:27,333 THEM FLEXIBILITY TO ADJUST THEIR 2755 02:11:27,333 --> 02:11:28,401 SCIENTIFIC AIMS WITHIN THE SCOPE 2756 02:11:28,401 --> 02:11:31,804 OF THE GRANT TO ALLOW THEM TO 2757 02:11:31,804 --> 02:11:33,773 INCORPORATE THE CHANGES THAT HAD 2758 02:11:33,773 --> 02:11:36,375 OCCURRED IN THE PANDEMIC OVER 2759 02:11:36,375 --> 02:11:36,576 TIME. 2760 02:11:36,576 --> 02:11:38,744 SO FOR INSTANCE THE RAPID 2761 02:11:38,744 --> 02:11:40,846 AVAILABILITY OF VACCINES WAS 2762 02:11:40,846 --> 02:11:42,715 NECESSITATING TO LOOK AT THE 2763 02:11:42,715 --> 02:11:44,417 RESPONSE TO VACCINATION. 2764 02:11:44,417 --> 02:11:47,219 AND TO LOOK AT THE EFFECT ON 2765 02:11:47,219 --> 02:11:49,188 LONGITUDINAL COHORTS. 2766 02:11:49,188 --> 02:11:50,590 THE APPARENT OF VIRAL VARIANTS 2767 02:11:50,590 --> 02:11:52,291 WAS ALLOWED TO BE INCORPORATED 2768 02:11:52,291 --> 02:11:54,760 IN THEIR STUDIES AND HOW THOSE 2769 02:11:54,760 --> 02:11:56,529 EFFECTED THE IMMUNE RESPONSE AND 2770 02:11:56,529 --> 02:11:58,798 FINALLY WITH THE APPEARANCE OF 2771 02:11:58,798 --> 02:12:00,866 LONG COACHED, THAT WORK WAS ALSO 2772 02:12:00,866 --> 02:12:01,667 ALLOWED TO BE INCORPORATED IN 2773 02:12:01,667 --> 02:12:07,640 THE GRANTS. 2774 02:12:07,640 --> 02:12:13,245 SO I THINK IF YOU LOOK OVERALL, 2775 02:12:13,245 --> 02:12:16,916 SERONET WAS HIGHLY SUCCESSFUL 2776 02:12:16,916 --> 02:12:17,283 SCIENTIFICALLY. 2777 02:12:17,283 --> 02:12:18,551 LOOKING AT THREE BROAD 2778 02:12:18,551 --> 02:12:19,452 CATEGORIES OVER THE NEXT THREE 2779 02:12:19,452 --> 02:12:21,053 SLIDES AND A NUMBER OF THE 2780 02:12:21,053 --> 02:12:23,756 INVESTIGATORS WERE LOOKING AT 2781 02:12:23,756 --> 02:12:28,127 THE IMMUNE RESPONSE TO SARS COV2 2782 02:12:28,127 --> 02:12:31,564 AND ITS VARIANTS IN THE GENERAL 2783 02:12:31,564 --> 02:12:34,166 POPULATION AS WELL AS THE 2784 02:12:34,166 --> 02:12:36,869 RESPONSE THE IMMUNE RESPONSE TO 2785 02:12:36,869 --> 02:12:39,805 VACCINATION AND HOW THE RESPONSE 2786 02:12:39,805 --> 02:12:40,306 TO VACCINE AND VIRUSES 2787 02:12:40,306 --> 02:12:45,177 DELIVERED. 2788 02:12:45,177 --> 02:12:46,779 OTHER INVESTIGATORS WERE LOOKING 2789 02:12:46,779 --> 02:12:49,382 AT THE VACCINE RESPONSES AND 2790 02:12:49,382 --> 02:12:51,584 COMMUNICATIONS WITH CANCER TO 2791 02:12:51,584 --> 02:12:54,754 SEE HOW CANCER PATIENTS THOSE 2792 02:12:54,754 --> 02:13:00,726 WHO EITHER HADN'T BEEN OR HAD 2793 02:13:00,726 --> 02:13:03,529 BEEN UNDER THERAPY WOULD RESPOND 2794 02:13:03,529 --> 02:13:05,164 AND RESPONSES WERE OBSERVED IN 2795 02:13:05,164 --> 02:13:06,399 CANCER PATIENTS BUT 2796 02:13:06,399 --> 02:13:07,500 INTERESTINGLY, THIS WAS REALLY 2797 02:13:07,500 --> 02:13:10,670 THE FIRST STUDY THAT HAD EVER 2798 02:13:10,670 --> 02:13:11,270 BEEN DONE IN RESPONSE TO ANY 2799 02:13:11,270 --> 02:13:15,608 VACCINE. 2800 02:13:15,608 --> 02:13:17,009 THAT'S WITH PATIENTS WITH 2801 02:13:17,009 --> 02:13:17,276 CANCER. 2802 02:13:17,276 --> 02:13:19,745 WHAT WE LEARNED HERE WILL BE 2803 02:13:19,745 --> 02:13:21,347 APPLICABLE BEYOND WHAT WE JUST 2804 02:13:21,347 --> 02:13:31,757 LEARNED ABOUT SARS COV2. 2805 02:13:33,526 --> 02:13:37,563 THE FINAL WAS LOOKING AT THE 2806 02:13:37,563 --> 02:13:41,000 VACCINE RESPONSES IN OTHER 2807 02:13:41,000 --> 02:13:46,005 REPRESENTATIONS IN 2808 02:13:46,005 --> 02:13:50,743 IMMUNOCOMPROMISEDD INFLAMMATION 2809 02:13:50,743 --> 02:13:52,344 MAY EFFECT THE RESPONSE TO THE 2810 02:13:52,344 --> 02:13:53,212 VACCINE. 2811 02:13:53,212 --> 02:13:56,549 FROM THIS QUICK OVERVIEW OF THE 2812 02:13:56,549 --> 02:13:59,985 SCIENCE IN SERONET IT'S BEEN A 2813 02:13:59,985 --> 02:14:01,187 HIGHLY SUCCESSFUL PROGRAM BUT 2814 02:14:01,187 --> 02:14:02,822 TRYING TO LOOK AT IT MORE 2815 02:14:02,822 --> 02:14:07,960 OBJECTIVE WE CAN ASK WHAT IMPACT 2816 02:14:07,960 --> 02:14:09,361 HAS THIS PROGRAM HAD ON THE 2817 02:14:09,361 --> 02:14:10,096 BROADER COMMUNITY AND THAT'S 2818 02:14:10,096 --> 02:14:15,568 SHOWN IN THE NEXT SLIDE WHEN WE 2819 02:14:15,568 --> 02:14:23,609 LOOK AT THE SERONET PUBLISHED 2820 02:14:23,609 --> 02:14:25,244 ARTICLES AND WHEN WE WORK WITH 2821 02:14:25,244 --> 02:14:30,216 THE TOP 1% OF ARTICLES THAT ARE 2822 02:14:30,216 --> 02:14:32,118 CITED, THAT SERONET RANKS ABOVE 2823 02:14:32,118 --> 02:14:33,886 THE OTHER COMPARATIVE GROUPS IN 2824 02:14:33,886 --> 02:14:38,724 THE FREQUENCY OF APPEARING IN 2825 02:14:38,724 --> 02:14:44,497 THE TOP 1%. 2826 02:14:44,497 --> 02:14:46,899 AND I'D LIKE TO THANK ALL THE 2827 02:14:46,899 --> 02:14:53,572 PEOPLE WHO HAVE BEEN INVOLVED 2828 02:14:53,572 --> 02:14:56,041 ESPECIALLY SAM AND JUDY AND 2829 02:14:56,041 --> 02:15:00,146 OTHERS FOR THEIR INCREDIBLE 2830 02:15:00,146 --> 02:15:02,515 EFFORT AND OTHERS WERE CRYSTAL 2831 02:15:02,515 --> 02:15:04,884 AND TACTIC AND THE REST OF THE 2832 02:15:04,884 --> 02:15:09,188 NCI STAFF WERE INVOLVED. 2833 02:15:09,188 --> 02:15:10,990 I THINK RATHER THAN THE 2834 02:15:10,990 --> 02:15:14,593 QUESTIONS RIGHT NOW WE GO TO THE 2835 02:15:14,593 --> 02:15:16,762 NEXT SLIDE I'D LIKE TO HAND THE 2836 02:15:16,762 --> 02:15:17,930 PRESENTATION TO DR. PINTO WHO 2837 02:15:17,930 --> 02:15:23,068 WILL TELL YOU ABOUT THE AMAZING 2838 02:15:23,068 --> 02:15:33,546 EFFORTS OF THE FNL SEROLOGY 2839 02:15:40,319 --> 02:15:40,486 CENTER. 2840 02:15:40,486 --> 02:15:40,820 >> THANK YOU. 2841 02:15:40,820 --> 02:15:42,221 IT'S A PLEASURE TO BE WITH YOU 2842 02:15:42,221 --> 02:15:43,022 ALL TODAY. 2843 02:15:43,022 --> 02:15:45,758 THANK YOU SO MUCH FOR THE 2844 02:15:45,758 --> 02:15:52,298 INVITATION TO PRESENT ON SOME OF 2845 02:15:52,298 --> 02:15:56,068 OUR WORK IN SERONET TO SUPPORT 2846 02:15:56,068 --> 02:15:58,737 THE NCI RESPONSE TO THE COVID-19 2847 02:15:58,737 --> 02:16:03,142 PANDEMIC. 2848 02:16:03,142 --> 02:16:08,480 WE'RE UNDER THE SCIENCE AND 2849 02:16:08,480 --> 02:16:10,749 TECHNOLOGY GROUP AT FNL 2850 02:16:10,749 --> 02:16:12,952 INCLUDING THE SEROLOGY 2851 02:16:12,952 --> 02:16:17,256 LABORATORY AND IMMUNOPREVENTION 2852 02:16:17,256 --> 02:16:24,129 LABORATORY AND TWO INITIATIVES. 2853 02:16:24,129 --> 02:16:25,531 THE SARS COV2 SEROLOGICAL 2854 02:16:25,531 --> 02:16:28,534 NETWORK AND THE SEROLOGY LAB AND 2855 02:16:28,534 --> 02:16:29,068 THE COORDINATING CENTER 2856 02:16:29,068 --> 02:16:33,706 DR. SINGER WAS REFERRED TO AND A 2857 02:16:33,706 --> 02:16:36,308 CENTER FOR EXCELLENCE FOR 2858 02:16:36,308 --> 02:16:40,946 SEROLOGY DEVELOPMENT AND 2859 02:16:40,946 --> 02:16:41,881 EMERGENCY REPAIPREPAREDNESS. 2860 02:16:41,881 --> 02:16:44,183 THE MISSION OF THE GROUP IS TO 2861 02:16:44,183 --> 02:16:47,219 STUDY IMMUNE RESPONSES TO HUMAN 2862 02:16:47,219 --> 02:16:49,321 PAPILLOMA VIRUS AND SARS COV2 2863 02:16:49,321 --> 02:16:52,324 INFECTION AND VACCINES AS WELL 2864 02:16:52,324 --> 02:16:53,626 AS OTHER CANCER PREVENTION 2865 02:16:53,626 --> 02:16:55,828 STRATEGIES IN THE CONTEXT OF 2866 02:16:55,828 --> 02:16:57,563 CLINICAL AND PRECLINICAL 2867 02:16:57,563 --> 02:16:57,796 STUDIES. 2868 02:16:57,796 --> 02:17:01,333 ALWAYS WITH THE GOAL OF 2869 02:17:01,333 --> 02:17:01,967 TRANSLATING LABORATORY SCIENCE 2870 02:17:01,967 --> 02:17:05,337 INTO PUBLIC HEALTH BENEFIT. 2871 02:17:05,337 --> 02:17:07,439 WE HAVE BEEN WORKING FOR THE 2872 02:17:07,439 --> 02:17:13,078 PAST TWO DECADES ON IMMUNOLOGY 2873 02:17:13,078 --> 02:17:13,579 AND SEROLOGY. 2874 02:17:13,579 --> 02:17:15,614 AND OUR WORK INCLUDES SUPPORT 2875 02:17:15,614 --> 02:17:18,751 FOR NCI VACCINE TRIALS AND 2876 02:17:18,751 --> 02:17:21,387 LAUNCH EPILOGICAL STUDIES AND WE 2877 02:17:21,387 --> 02:17:26,358 COLLABORATE EXTENSIVELY WITH THE 2878 02:17:26,358 --> 02:17:30,029 EXTRAMURAL COMMUNITY AND WE ARE 2879 02:17:30,029 --> 02:17:32,298 LEADING THE HPV STANDARD 2880 02:17:32,298 --> 02:17:35,367 INITIATIVE SERVING AS THE 2881 02:17:35,367 --> 02:17:38,737 CENTRAL REFERENCE LAB WITH 2882 02:17:38,737 --> 02:17:40,773 SEVERAL PARTNERS ACROSS THE 2883 02:17:40,773 --> 02:17:43,375 GLOBE THE BILL AND MELINDA GATES 2884 02:17:43,375 --> 02:17:44,543 FOUNDATION AND THE NATIONAL 2885 02:17:44,543 --> 02:17:46,211 INSTITUTES FOR BIOLOGICAL 2886 02:17:46,211 --> 02:17:53,552 STANDARDS AND CONTROL IN THE 2887 02:17:53,552 --> 02:17:54,753 U.K., VARIOUS INSTITUTES AND 2888 02:17:54,753 --> 02:17:55,587 WHL. 2889 02:17:55,587 --> 02:17:59,258 WE'RE A WHL REFERENCE LABORATORY 2890 02:17:59,258 --> 02:18:02,194 AND DURING THE EPIDEMIC WE SE 2891 02:18:02,194 --> 02:18:03,963 SERSER 2892 02:18:03,963 --> 02:18:07,099 SERVED AS AN FDA TESTING 2893 02:18:07,099 --> 02:18:10,336 LABORA 2894 02:18:10,336 --> 02:18:11,804 LABORATORY FOR THE COMMUNITY. 2895 02:18:11,804 --> 02:18:13,105 OUR LABORATORY PLAYED A CRITICAL 2896 02:18:13,105 --> 02:18:15,374 ROLE IN UNDERSTANDING HOW HPV 2897 02:18:15,374 --> 02:18:16,342 VACCINES WORK. 2898 02:18:16,342 --> 02:18:19,078 WE WERE ONE OF THE FIRST FEW 2899 02:18:19,078 --> 02:18:19,812 LABS TO DEMONSTRATE LONG-TERM 2900 02:18:19,812 --> 02:18:23,415 ANTIBODY RESPONSES FOR A SINGLE 2901 02:18:23,415 --> 02:18:25,584 DOSE OF HPV VACCINE SUGGESTING 2902 02:18:25,584 --> 02:18:29,722 THIS SINGLE DOSE MAY BE AS 2903 02:18:29,722 --> 02:18:31,590 EFFECTIVE AS THE RECOMMENDED AND 2904 02:18:31,590 --> 02:18:34,693 APPROVED TWO AND THREE-DOSE 2905 02:18:34,693 --> 02:18:34,960 SCHEDULES. 2906 02:18:34,960 --> 02:18:36,662 AND WITH INCREASING NUMBER OF 2907 02:18:36,662 --> 02:18:40,966 TRIALS FOR NOVEL HPV VACCINE 2908 02:18:40,966 --> 02:18:44,103 REGIMENT RECOMMENDATIONS AND 2909 02:18:44,103 --> 02:18:47,439 VACCINES, WE RELIED ON SEROLOGY 2910 02:18:47,439 --> 02:18:50,009 AS END POINT IN BRIDGING TRIALS 2911 02:18:50,009 --> 02:18:53,112 TO INFORM REGULATORY DECISIONS. 2912 02:18:53,112 --> 02:18:58,217 WE FELT THERE WAS AN URGENT NEED 2913 02:18:58,217 --> 02:19:00,219 AS THERE WAS NO STANDARDIZED 2914 02:19:00,219 --> 02:19:02,955 ASSAYS OR PROCEDURES. 2915 02:19:02,955 --> 02:19:05,190 TO ADDRESS THIS WELL RECOGNIZED 2916 02:19:05,190 --> 02:19:06,658 STANDARDIZATION GAP, WE 2917 02:19:06,658 --> 02:19:09,495 ESTABLISHED THE HPV SEROLOGY 2918 02:19:09,495 --> 02:19:10,095 STANDARDIZATION INITIATIVE IB 2919 02:19:10,095 --> 02:19:17,369 202127 -- IN 2017 AND SPONSORED 2920 02:19:17,369 --> 02:19:19,605 BY THE NCI AND GATES FOUNDATION. 2921 02:19:19,605 --> 02:19:20,906 REALLY THE MISSION OF THIS 2922 02:19:20,906 --> 02:19:25,444 INITIATIVE IS TO WORK IN 2923 02:19:25,444 --> 02:19:26,645 PARTNERSHIP WITH THE 2924 02:19:26,645 --> 02:19:28,547 INTERNATIONAL HPV COMMUNITY TO 2925 02:19:28,547 --> 02:19:30,749 PROMOTE FURTHER STANDARDIZATION 2926 02:19:30,749 --> 02:19:36,088 AND ORGANIZATION AND PROFICIENCY 2927 02:19:36,088 --> 02:19:38,490 TO ESTABLISH FACTS IN 2928 02:19:38,490 --> 02:19:39,058 IMMUNOGENICITY IN CLINICAL 2929 02:19:39,058 --> 02:19:39,291 TRIAL. 2930 02:19:39,291 --> 02:19:41,193 WE DO THIS THROUGH THE 2931 02:19:41,193 --> 02:19:43,362 DEVELOPMENT OF QUALIFIED ASSAY 2932 02:19:43,362 --> 02:19:46,765 STANDARDS, CRITICAL RE-AGENTS 2933 02:19:46,765 --> 02:19:49,768 AND THE EMPHASIS TO LOOK AT 2934 02:19:49,768 --> 02:19:53,005 ANTIBODY RESPONSES THROUGH THE 2935 02:19:53,005 --> 02:19:54,740 DEVELOPMENT OF MULTIPLEX HIGH 2936 02:19:54,740 --> 02:19:57,176 THROUGHPUT ASSAYS THAT WE MAKE 2937 02:19:57,176 --> 02:19:58,610 ALL AVAILABLE TO THE SCIENTIFIC 2938 02:19:58,610 --> 02:20:01,613 COMMUNITY AT OUR WEBSITE LISTED 2939 02:20:01,613 --> 02:20:08,787 BELOW. 2940 02:20:08,787 --> 02:20:10,823 WITH HAVE CAPABILITY FOR 2941 02:20:10,823 --> 02:20:11,423 CLINICAL TRIALS AND HOPE BY 2942 02:20:11,423 --> 02:20:16,829 DOING THIS BIG THE SCIENTIFIC 2943 02:20:16,829 --> 02:20:19,231 COMMUNITY WE ARE ABLE TO THEN TO 2944 02:20:19,231 --> 02:20:20,766 COMPARE RESULTS FROM DIFFERENT 2945 02:20:20,766 --> 02:20:22,334 VACCINES IN A MANNER NOT 2946 02:20:22,334 --> 02:20:26,738 POSSIBLE BEFORE AND CELEBRATED 2947 02:20:26,738 --> 02:20:28,173 IMPLEMENTATION OF NEW VACCINES 2948 02:20:28,173 --> 02:20:29,741 AND RECOMMENDATIONS. 2949 02:20:29,741 --> 02:20:31,777 AND AS MENTIONED EARLIER WE'RE 2950 02:20:31,777 --> 02:20:33,846 DOING THIS IN COLLABORATION WITH 2951 02:20:33,846 --> 02:20:38,717 A LARGE NUMBER OF PARTNERS AND 2952 02:20:38,717 --> 02:20:42,721 NCI AND GATES FOUNDATION AND CDC 2953 02:20:42,721 --> 02:20:45,324 AND PUBLIC HEALTH ENGLAND AND 2954 02:20:45,324 --> 02:20:46,425 THE NATIONAL INSTITUTES OF 2955 02:20:46,425 --> 02:20:49,194 BIOLOGICAL STANDARDS AND CONTROL 2956 02:20:49,194 --> 02:20:50,195 AS WELL AS A STRONG 2957 02:20:50,195 --> 02:20:55,701 COLLABORATION WITH MANY ACADEMIC 2958 02:20:55,701 --> 02:20:56,201 LABORATORIES AND OTHER 2959 02:20:56,201 --> 02:21:06,512 REGULATORY BODIES. 2960 02:21:09,381 --> 02:21:11,750 AND USING THE STANDARDIZED AND 2961 02:21:11,750 --> 02:21:14,720 VALIDATED ASSAYS, WE HAVE BEEN 2962 02:21:14,720 --> 02:21:15,287 CONDUCTING IMMUNOGENICITY 2963 02:21:15,287 --> 02:21:18,724 TESTING IN A LARGE NUMBER OF HPV 2964 02:21:18,724 --> 02:21:19,558 VACCINE TRIALS. 2965 02:21:19,558 --> 02:21:22,161 HERE IS A LIST OF SOME OF THE 2966 02:21:22,161 --> 02:21:23,595 ONE-DOSE TRIALS WE ARE 2967 02:21:23,595 --> 02:21:23,896 SUPPORTING. 2968 02:21:23,896 --> 02:21:28,066 WE HAVE CONDUCTED MORE THAN 2969 02:21:28,066 --> 02:21:30,135 100,000 TESTS ON ALL THE TRIALS. 2970 02:21:30,135 --> 02:21:33,772 YOU CAN SEE THESE TRIALS ARE 2971 02:21:33,772 --> 02:21:36,375 OCCURRING IN DIFFERENT PARTS OF 2972 02:21:36,375 --> 02:21:38,677 THE WORLD AND ALSO COVERING 2973 02:21:38,677 --> 02:21:42,714 DIFFERENT AGE GROUPS AND BOTH IN 2974 02:21:42,714 --> 02:21:50,722 GIRLS, WOMEN AND BOYS. 2975 02:21:50,722 --> 02:21:54,193 SO USING TECHNOLOGIES WE'VE BEEN 2976 02:21:54,193 --> 02:21:57,696 ABLE TO COMPARE DATA IN CLINICAL 2977 02:21:57,696 --> 02:21:58,363 TRIALS WHICH HAVE BEEN USED IN 2978 02:21:58,363 --> 02:22:00,232 PART FOR THE RECENT ENDORSEMENT 2979 02:22:00,232 --> 02:22:03,168 OF ONE DOSE OF HPV VACCINE BY 2980 02:22:03,168 --> 02:22:03,936 W.H.O. 2981 02:22:03,936 --> 02:22:07,039 WE BELIEVE THE STANDARDIZATION 2982 02:22:07,039 --> 02:22:14,012 IS THE KEY TO EVOLVE THE FIELD 2983 02:22:14,012 --> 02:22:15,847 TO FIGHT EFFECTIVELY AGAINST 2984 02:22:15,847 --> 02:22:17,583 CANCER AND POSSIBLY ELIMINATING 2985 02:22:17,583 --> 02:22:17,749 IT. 2986 02:22:17,749 --> 02:22:23,155 WITH ALL THE PARTNERSHIPS AND WE 2987 02:22:23,155 --> 02:22:26,258 WERE VERY WELL POSITIONED TO 2988 02:22:26,258 --> 02:22:29,595 RESPOND TO THE COVID PANDEMIC IN 2989 02:22:29,595 --> 02:22:31,964 MARCH 2020 WHEN WE WERE 2990 02:22:31,964 --> 02:22:35,000 APPROACHED BY THE NCI LEADERSHIP 2991 02:22:35,000 --> 02:22:37,336 AND WHY LOWY AND DR. SHARPLESS 2992 02:22:37,336 --> 02:22:40,105 TO DEVELOP SEROLOGY ASSAYS AND 2993 02:22:40,105 --> 02:22:42,241 ALSO DEVELOP STANDARDS FOR 2994 02:22:42,241 --> 02:22:43,442 SEROLOGY IN A MANNER THAT IS 2995 02:22:43,442 --> 02:22:46,278 SIMILAR TO WHAT WE WERE DOING 2996 02:22:46,278 --> 02:22:49,648 FOR THE HPV BECAUSE WE HAD BEEN 2997 02:22:49,648 --> 02:22:51,183 WORKING CLOSELY WITH W.H.O. FOR 2998 02:22:51,183 --> 02:22:54,753 THE INTERNATIONAL STANDARDS FOR 2999 02:22:54,753 --> 02:22:55,787 HPV. 3000 02:22:55,787 --> 02:22:57,356 SOON AFTER THAT FDA ASKED NCI 3001 02:22:57,356 --> 02:22:58,857 AND US TO HELP EVALUATE THE 3002 02:22:58,857 --> 02:23:01,727 QUALITY OF THE EMERGING 3003 02:23:01,727 --> 02:23:04,696 COMMERCIAL SEROLOGY DEVICES. 3004 02:23:04,696 --> 02:23:06,832 THEY WERE SUBMITTED TO FDA FOR 3005 02:23:06,832 --> 02:23:09,768 EMERGENCY USE AUTHORIZATION. 3006 02:23:09,768 --> 02:23:11,403 I HAVE TO SAY IT WAS AN AMAZING 3007 02:23:11,403 --> 02:23:13,805 EFFORT AND IT WAS EXCITING WAS 3008 02:23:13,805 --> 02:23:16,174 VERY LARGE AND INVOLVED SO MANY 3009 02:23:16,174 --> 02:23:21,847 HHS AGENCIES AND SO MANY 3010 02:23:21,847 --> 02:23:22,447 ACADEMIC LABORATORIES. 3011 02:23:22,447 --> 02:23:23,482 IT WAS A TREMENDOUS 3012 02:23:23,482 --> 02:23:24,950 COLLABORATION AND SOON AFTER 3013 02:23:24,950 --> 02:23:26,752 THAT AS DR. SINGER WAS 3014 02:23:26,752 --> 02:23:29,221 MENTIONING THERE WAS FUNDING 3015 02:23:29,221 --> 02:23:31,256 FROM HHS TO SUPPORT THE SARS 3016 02:23:31,256 --> 02:23:34,359 COV2 SEROLOGY INITIATIVES. 3017 02:23:34,359 --> 02:23:37,663 SO NOW I'D LIKE TO REVIEW SOME 3018 02:23:37,663 --> 02:23:40,432 OF OUR CONTRIBUTIONS AND 3019 02:23:40,432 --> 02:23:43,435 MILESTONES AT THE SEROLOGY LAB 3020 02:23:43,435 --> 02:23:44,703 RESPONSE TO THE COVID-19 3021 02:23:44,703 --> 02:23:47,639 PANDEMIC AND I HAVE TO REALLY 3022 02:23:47,639 --> 02:23:50,909 THANK DOCTORS CAMP AND RAUSCH 3023 02:23:50,909 --> 02:23:53,478 FOR THEIR LEADERSHIP IN THE 3024 02:23:53,478 --> 02:23:54,546 AREA. 3025 02:23:54,546 --> 02:23:58,717 WE HAVE A KEY ROLE IN THE 3026 02:23:58,717 --> 02:24:02,721 EVALUATION PROGRAM ESTABLISHED 3027 02:24:02,721 --> 02:24:06,258 BY FDA FOR SARS COV2 SEROLOGY 3028 02:24:06,258 --> 02:24:08,026 TEST AND VALIDATION PANELS WITH 3029 02:24:08,026 --> 02:24:11,163 WELL CHARACTERIZED PANELS TESTED 3030 02:24:11,163 --> 02:24:15,033 AGAINST MORE THAN 115 COMMERCIAL 3031 02:24:15,033 --> 02:24:16,501 TESTS. 3032 02:24:16,501 --> 02:24:20,038 AND SOME RECEIVED UA. 3033 02:24:20,038 --> 02:24:22,741 ONE THIRD RECEIVE UA AND IN SOME 3034 02:24:22,741 --> 02:24:25,110 CASES IT WAS REVOKED AND HAD A 3035 02:24:25,110 --> 02:24:27,746 KEY ROLE IN REDUCTION OF THE 3036 02:24:27,746 --> 02:24:31,283 SEROLOGY STANDARDS MORE THAN 185 3037 02:24:31,283 --> 02:24:31,917 REQUESTS IN THE UNITED STATES 3038 02:24:31,917 --> 02:24:34,052 AND GLOBALLY. 3039 02:24:34,052 --> 02:24:36,855 AND WE IMPLEMENTS A NUMBER OF 3040 02:24:36,855 --> 02:24:41,393 IMMUNOLOGICAL ASSAYS AND 3041 02:24:41,393 --> 02:24:42,728 VALIDATED A NUMBER OF THOSE 3042 02:24:42,728 --> 02:24:44,396 ASSAYS AND WE HAVE ESTABLISHED 3043 02:24:44,396 --> 02:24:49,668 AN 18 PLEX THAT INCLUDES ALL THE 3044 02:24:49,668 --> 02:24:53,372 VARIANTS AND ALSO THE COMMON 3045 02:24:53,372 --> 02:24:57,142 CORONAVIRUS AND WE'RE NOW IN THE 3046 02:24:57,142 --> 02:25:01,513 QUALIFICATION PHASE OF THE 3047 02:25:01,513 --> 02:25:04,049 ASSAYS WORKING CLOSELY WITH DUKE 3048 02:25:04,049 --> 02:25:04,883 UNIVERSITY. 3049 02:25:04,883 --> 02:25:07,686 SO USING THIS VALIDATED 3050 02:25:07,686 --> 02:25:10,355 TECHNOLOGIES WE DEVELOPED WE 3051 02:25:10,355 --> 02:25:11,923 INVESTIGATED IMMUNE RESPONSE TO 3052 02:25:11,923 --> 02:25:18,230 THE APPROVED VACCINES AND WE 3053 02:25:18,230 --> 02:25:22,734 TESTED MORE THAN 80,000 SAMPLE. 3054 02:25:22,734 --> 02:25:24,936 WE PLAYED A KEY ROLE IN 3055 02:25:24,936 --> 02:25:27,572 ESTABLISHING SERONET AND 3056 02:25:27,572 --> 02:25:31,777 MARCHING -- MANAGING THE DATA 3057 02:25:31,777 --> 02:25:37,215 CENTER AND THE MANAGEMENT OF THE 3058 02:25:37,215 --> 02:25:37,883 CAPACITY-BUILDING CENTERS WHICH 3059 02:25:37,883 --> 02:25:40,485 A COLLECTION OF A NUMBER OF 3060 02:25:40,485 --> 02:25:42,687 SPECIMENS FOR PRODUCTION OF 3061 02:25:42,687 --> 02:25:43,855 REFERENCE MATERIALS BUT ALSO 3062 02:25:43,855 --> 02:25:45,991 LONGITUDINAL STUDIES AND THE 3063 02:25:45,991 --> 02:25:48,693 MANAGEMENT OF HOW THAT PLAYED AS 3064 02:25:48,693 --> 02:25:53,331 WELL AS THE DATA OCCUR -- 3065 02:25:53,331 --> 02:25:55,167 CURATION DR. SINGER MENTIONED. 3066 02:25:55,167 --> 02:25:57,469 I ALSO WANT TO SPEND A COUPLE 3067 02:25:57,469 --> 02:25:59,771 MINUTES TALKING ABOUT THE 3068 02:25:59,771 --> 02:26:02,808 CLINICAL ENGINES OF THE SEROLOGY 3069 02:26:02,808 --> 02:26:06,745 TASK FORCE WE ESTABLISHED IN 3070 02:26:06,745 --> 02:26:09,181 FEBRUARY 2021. 3071 02:26:09,181 --> 02:26:10,315 THESE ARE THE PUBLICATIONS 3072 02:26:10,315 --> 02:26:13,151 RESULTING FROM THE WORK AND I 3073 02:26:13,151 --> 02:26:14,986 WOULD LIKE TO NOTE THIS 3074 02:26:14,986 --> 02:26:18,290 PUBLICATION FROM OUR COLLEAGUES 3075 02:26:18,290 --> 02:26:23,795 AT FDA HIGHLIGHTING THE EFFORT 3076 02:26:23,795 --> 02:26:28,733 MARK THE FIRST TIME IT 3077 02:26:28,733 --> 02:26:34,139 RECOMMENDED THIS TYPE OF 3078 02:26:34,139 --> 02:26:41,413 APPROACH FOR FUTURE PANDEMICS 3079 02:26:41,413 --> 02:26:44,282 I'D LIKE TO SPEND A MINUTE 3080 02:26:44,282 --> 02:26:46,451 TALKING ABOUT THE SPECIMENS BY 3081 02:26:46,451 --> 02:26:49,421 THE CAPACITY BUILDING CENTERS. 3082 02:26:49,421 --> 02:26:51,156 AND WHAT IS INTERESTING ABOUT 3083 02:26:51,156 --> 02:26:56,595 THIS IS THAT WE HAVE REALLY BOTH 3084 02:26:56,595 --> 02:26:58,864 SERUM AND PERIPHERAL BLOOD IN 3085 02:26:58,864 --> 02:27:02,400 OUR CELLS CRYO PRESERVED FROM 3086 02:27:02,400 --> 02:27:04,503 HEALTHY INDIVIDUALS AS WELL AS 3087 02:27:04,503 --> 02:27:06,171 INDIVIDUALS WITH CANCER, AUTO 3088 02:27:06,171 --> 02:27:07,372 IMMUNITY AND SOME TRANSPLANT 3089 02:27:07,372 --> 02:27:16,882 RECIPIENTS AND HIV. 3090 02:27:16,882 --> 02:27:20,719 AND USING THE SAME SAMPLE 3091 02:27:20,719 --> 02:27:22,954 PROCESSING AND ALSO THE SAME 3092 02:27:22,954 --> 02:27:24,389 DATA ELEMENTS. 3093 02:27:24,389 --> 02:27:28,093 THE PARTICIPANT ENROLLMENTS 3094 02:27:28,093 --> 02:27:30,829 STARTED IN 2021 AND WENT UNTIL 3095 02:27:30,829 --> 02:27:32,063 EARLY 2024. 3096 02:27:32,063 --> 02:27:34,432 AND THE SAMPLES HAVE BEEN USED 3097 02:27:34,432 --> 02:27:37,702 BY THE SEROLOGY LAB FOR A NUMBER 3098 02:27:37,702 --> 02:27:42,707 OF STUDIES ONGOING AS WELL AS TO 3099 02:27:42,707 --> 02:27:43,842 SERONET MEMBERS AND WANT TO 3100 02:27:43,842 --> 02:27:46,711 EMPHASIZE THE REACH, COLLECTION, 3101 02:27:46,711 --> 02:27:50,882 TIME POINTS WE HAVE HERE AFTER 3102 02:27:50,882 --> 02:27:53,685 VACCINATION OR INFECTION AND WE 3103 02:27:53,685 --> 02:27:58,456 HAD MANY VACCINES AND ALSO 3104 02:27:58,456 --> 02:28:00,559 BREAKTHROUGH INFECTIONS THAT 3105 02:28:00,559 --> 02:28:03,428 REALLY WE HAVE TO START/RESTART 3106 02:28:03,428 --> 02:28:04,629 THE TIME LINE AS NEW EVENTS WERE 3107 02:28:04,629 --> 02:28:06,164 OCCURRING. 3108 02:28:06,164 --> 02:28:10,235 I WANT TO EMPHASIZE THIS WAS 3109 02:28:10,235 --> 02:28:11,903 DONE REALLY THE POWER OF 3110 02:28:11,903 --> 02:28:13,171 COLLABORATION AND THE IMPRESSIVE 3111 02:28:13,171 --> 02:28:19,210 TIME LINE OF ACHIEVEMENTS WITH 3112 02:28:19,210 --> 02:28:22,847 THE NCI AND THE LABS AND THE 3113 02:28:22,847 --> 02:28:24,215 MATERIALS ARRIVED IN THE 3114 02:28:24,215 --> 02:28:29,354 LABORATORY AT THE END OF MARCH 3115 02:28:29,354 --> 02:28:32,924 AND USING OUR PLUG AND PLAY 3116 02:28:32,924 --> 02:28:34,092 TECHNOLOGIES WE WERE ABLE TO 3117 02:28:34,092 --> 02:28:37,729 HAVE THE ASSAYS IMPLEMENTS 3118 02:28:37,729 --> 02:28:39,197 WITHIN ONE TO TWO WEEKS AFTER 3119 02:28:39,197 --> 02:28:45,203 THE PROTEIN GENERATION WHICH WAS 3120 02:28:45,203 --> 02:28:46,671 AN AMAZING ASSET WE HAVE HERE 3121 02:28:46,671 --> 02:28:49,574 AND ALLOWED IT TO MOVE FAST AND 3122 02:28:49,574 --> 02:28:53,979 GRANTS FROM THE NCI AND 3123 02:28:53,979 --> 02:28:54,613 CONTRACTS AWARDED VERY SOON 3124 02:28:54,613 --> 02:28:58,683 AFTER THE RFAs WERE PUBLISHED 3125 02:28:58,683 --> 02:29:00,585 AND FUNDING WAS RECEIVED. 3126 02:29:00,585 --> 02:29:01,853 IT WAS AN AMAZING EXAMPLE OF THE 3127 02:29:01,853 --> 02:29:06,458 COLLABORATION. 3128 02:29:06,458 --> 02:29:08,994 I WOULD LIKE TO EMPHASIZE ALSO 3129 02:29:08,994 --> 02:29:10,562 ANOTHER ACHIEVEMENT AND REALLY A 3130 02:29:10,562 --> 02:29:12,197 PLEASURE THAT HAS BEEN WORKING 3131 02:29:12,197 --> 02:29:14,633 WITH ALL THE COLLEAGUES FROM SO 3132 02:29:14,633 --> 02:29:17,402 MANY ORGANIZATIONS ON THE 3133 02:29:17,402 --> 02:29:20,238 CLINICAL AND TRANSLATIONAL 3134 02:29:20,238 --> 02:29:25,610 SEROLOGY TASK FORCE CO-CHAIRED 3135 02:29:25,610 --> 02:29:32,017 WITH DR. SARGO AT MOUNT SINAI 3136 02:29:32,017 --> 02:29:34,352 AND WE'RE STILL MEETING AND WE 3137 02:29:34,352 --> 02:29:37,355 ORGANIZED MORE THAN 64 MEETINGS 3138 02:29:37,355 --> 02:29:43,962 AND ONE WORKSHOP AS WELL AND WE 3139 02:29:43,962 --> 02:29:44,295 HA 3140 02:29:44,295 --> 02:29:47,499 HAVE THE SERONEWS WE PUBLISH. 3141 02:29:47,499 --> 02:29:49,734 THE COURSE OF THE TASK FORCE WAS 3142 02:29:49,734 --> 02:29:52,303 BRINGING TOGETHER AND ENGAGING 3143 02:29:52,303 --> 02:29:53,304 VARIOUS GOVERNMENT ORGANIZATIONS 3144 02:29:53,304 --> 02:29:56,241 SO ALL THE COLLABORATORS WE WERE 3145 02:29:56,241 --> 02:29:58,710 WORKING WITH FROM CDC, FDA, THE 3146 02:29:58,710 --> 02:30:00,845 ACADEMIC GROUPS, INDUSTRY 3147 02:30:00,845 --> 02:30:02,280 PARTNERS BECAUSE WE WORKED WITH 3148 02:30:02,280 --> 02:30:05,550 SEVERAL INDUSTRY PARTNERS ALSO 3149 02:30:05,550 --> 02:30:07,585 DURING THE PANDEMIC TO PROVIDE 3150 02:30:07,585 --> 02:30:11,222 TOOLS AND INFORMATION RELATED TO 3151 02:30:11,222 --> 02:30:13,158 SEROLOGY TESTING AND DEVELOPMENT 3152 02:30:13,158 --> 02:30:15,360 AND HELP DECISION MAKERS MANAGE 3153 02:30:15,360 --> 02:30:16,494 THE CURRENT AND FUTURE STATUS OF 3154 02:30:16,494 --> 02:30:17,462 THE PANDEMIC. 3155 02:30:17,462 --> 02:30:21,633 YOU CAN SEE HERE THE LINK TO THE 3156 02:30:21,633 --> 02:30:25,236 VARIOUS SERONEWS WE PUBLISHED. 3157 02:30:25,236 --> 02:30:29,841 I WANT TO EMPHASIZE TWO OF THE 3158 02:30:29,841 --> 02:30:32,410 OUTCOMES OF THE CLINICAL AND 3159 02:30:32,410 --> 02:30:34,279 TRANSLATIONAL TASK FORCE AND 3160 02:30:34,279 --> 02:30:37,315 WE'RE PROUD OF THIS WORK WORKING 3161 02:30:37,315 --> 02:30:40,085 AGAIN CLOSELY TOGETHER AND 3162 02:30:40,085 --> 02:30:41,786 ILLUSTRATING THE POWER OF 3163 02:30:41,786 --> 02:30:42,053 CONVENING. 3164 02:30:42,053 --> 02:30:45,690 ONE WAS THE REAL WORLD DATA 3165 02:30:45,690 --> 02:30:46,858 INFRASTRUCTURE THAT WAS 3166 02:30:46,858 --> 02:30:49,761 DEVELOPED TO EVALUATE THE IMPACT 3167 02:30:49,761 --> 02:30:51,996 OF INFECTION AND VACCINE 3168 02:30:51,996 --> 02:30:54,099 EFFECTIVENESS IN HEALTHY 3169 02:30:54,099 --> 02:30:56,434 INDIVIDUALS AND 3170 02:30:56,434 --> 02:30:58,103 IMMUNOCOMPROMISIZED INDIVIDUALS 3171 02:30:58,103 --> 02:30:59,471 WITH AN EMPHASIS ON CANCER 3172 02:30:59,471 --> 02:31:04,008 PATIENT AND THE WORK IS BEING 3173 02:31:04,008 --> 02:31:09,614 LED BY DR. BEN BURKE AND 3174 02:31:09,614 --> 02:31:11,082 NORTHWELL AND I WANT TO THEM 3175 02:31:11,082 --> 02:31:11,916 THEM FOR THAT. 3176 02:31:11,916 --> 02:31:13,118 THIS IS AN AMAZING 3177 02:31:13,118 --> 02:31:14,753 INFRASTRUCTURE FILLING AN 3178 02:31:14,753 --> 02:31:18,690 AMAZING GAP WE LAD AND THE 3179 02:31:18,690 --> 02:31:21,760 CENTER OF EXCELLENCE FOR SAMPLE 3180 02:31:21,760 --> 02:31:23,928 ACQUISITION WICK BIO SPECIMENS 3181 02:31:23,928 --> 02:31:26,731 THAT WILL BE WELL CHARACTERIZED 3182 02:31:26,731 --> 02:31:30,201 AND ANNOTATED AND HIGH QUALITY 3183 02:31:30,201 --> 02:31:33,238 SEROLOGY AND OTHER IMMUNOLOGICAL 3184 02:31:33,238 --> 02:31:35,140 TESTING WHERE WE ARE INTERESTED 3185 02:31:35,140 --> 02:31:37,275 IN STANDARDIZING T CELL ASSAYS 3186 02:31:37,275 --> 02:31:39,944 NOW AND WORKING CLOSELY WITH 3187 02:31:39,944 --> 02:31:43,748 DR. AHMED TO ACHIEVE AND BRING 3188 02:31:43,748 --> 02:31:44,816 THEM TO THE SAME LEVEL WE HAVE 3189 02:31:44,816 --> 02:31:48,286 WITH SEROLOGY THAT CAN BE USED 3190 02:31:48,286 --> 02:31:52,123 TO INFORM REGULATORY DECISIONS 3191 02:31:52,123 --> 02:31:53,992 AND FOR PUBLIC HEALTH BENEFIT. 3192 02:31:53,992 --> 02:31:57,629 SO JUST A COUPLE OF SLIDES ON 3193 02:31:57,629 --> 02:32:07,739 THE CENTER OF EXCELLENCE TO 3194 02:32:07,739 --> 02:32:10,275 CONTROL FUTURE AND CURRENT 3195 02:32:10,275 --> 02:32:12,811 OUTBREAKS AND ADDRESSING GAPS IN 3196 02:32:12,811 --> 02:32:14,112 STANDARDIZATION IN FAST 3197 02:32:14,112 --> 02:32:15,713 DEVELOPMENT AND DEVELOPMENT OF 3198 02:32:15,713 --> 02:32:20,852 ASSAYS THAT CAN BE USED TO 3199 02:32:20,852 --> 02:32:22,720 PROVIDE ACCURATE INFORMATION TO 3200 02:32:22,720 --> 02:32:23,755 VACCINATION TO SERVE THE PUBLIC 3201 02:32:23,755 --> 02:32:26,624 HEALTH NEEDS OF HEALTHY 3202 02:32:26,624 --> 02:32:30,028 INDIVIDUALS AND OF COURSE VERY 3203 02:32:30,028 --> 02:32:31,629 INTERESTED WITH POPULATIONS IN 3204 02:32:31,629 --> 02:32:33,565 PARTICULAR IN PEOPLE WITH 3205 02:32:33,565 --> 02:32:33,798 CANCER. 3206 02:32:33,798 --> 02:32:36,000 AND THE APPROACH IS REALLY 3207 02:32:36,000 --> 02:32:36,267 PROGRESS. 3208 02:32:36,267 --> 02:32:38,970 IT'S THE WAY WE HAVE TO DO 3209 02:32:38,970 --> 02:32:40,738 THINGS IS WORK TOGETHER AS WE 3210 02:32:40,738 --> 02:32:46,077 WORKED FROM THE BEGINNING OF THE 3211 02:32:46,077 --> 02:32:47,879 PANDEMIC AND ALSO WITHIN 3212 02:32:47,879 --> 02:32:50,715 CLINICAL CENTERS WITH THE 3213 02:32:50,715 --> 02:32:51,749 CAPABILITIES TO PROVIDE LARGE 3214 02:32:51,749 --> 02:32:54,752 BLOOD COLLECTIONS AS WELL AS 3215 02:32:54,752 --> 02:32:58,156 TESTING CENTERS THAT CAN DO HIGH 3216 02:32:58,156 --> 02:32:59,924 THROUGHPUT TESTING IN AN 3217 02:32:59,924 --> 02:33:01,626 EFFICIENT MANNER AND DOING THAT 3218 02:33:01,626 --> 02:33:02,994 THROUGH ESTABLISHMENT OF 3219 02:33:02,994 --> 02:33:06,130 CONTRACTS AND OF COURSE HUGE 3220 02:33:06,130 --> 02:33:08,199 COLLABORATION ACROSS OUR 3221 02:33:08,199 --> 02:33:12,036 DIRECTORATES. 3222 02:33:12,036 --> 02:33:15,173 THIS IS EMPHASIZING BIG PROBLEMS 3223 02:33:15,173 --> 02:33:17,642 AND BOTTLENECKS AT THIS 3224 02:33:17,642 --> 02:33:19,477 BEGINNING OF THE PANDEMIC AND 3225 02:33:19,477 --> 02:33:21,145 LACK OF SAMPLES AND LACK OF 3226 02:33:21,145 --> 02:33:26,351 STANDARDS AND GUIDELINES AND 3227 02:33:26,351 --> 02:33:30,154 THAT CREATED SOME PROBLEMS IN 3228 02:33:30,154 --> 02:33:33,658 UNDERSTANDING WHAT IS THE IMMUNE 3229 02:33:33,658 --> 02:33:36,494 RESPONSE IN INFECTION TO THE 3230 02:33:36,494 --> 02:33:37,795 VACCINE AND WE'RE BUILDING A 3231 02:33:37,795 --> 02:33:40,031 STRONG NETWORK OF PARTNERS WITH 3232 02:33:40,031 --> 02:33:41,466 THE EXPERTISE AND CAPABILITIES 3233 02:33:41,466 --> 02:33:44,102 AS WELL AS DEVELOP A 3234 02:33:44,102 --> 02:33:45,837 STANDARDIZED DATA MANAGEMENT 3235 02:33:45,837 --> 02:33:47,272 INFRASTRUCTURE AND MAKING THE 3236 02:33:47,272 --> 02:33:50,341 TOOLS WE PRODUCE AVAILABLE TO 3237 02:33:50,341 --> 02:33:52,443 SCIENTIFIC COMMUNITY OUR GOAL IS 3238 02:33:52,443 --> 02:33:55,013 TO DO THAT THROUGH A PORTAL THAT 3239 02:33:55,013 --> 02:33:59,584 IS CURRENTLY UNDER DEVELOPMENT. 3240 02:33:59,584 --> 02:34:01,152 IN TERMS OF LONG-TERM PLANS WE 3241 02:34:01,152 --> 02:34:02,587 THINK WE NEED TO SUSTAIN THIS 3242 02:34:02,587 --> 02:34:06,724 TYPE OF CAPABILITIES AND WE NEED 3243 02:34:06,724 --> 02:34:10,728 TO LEVERAGE THE ESTABLISHED 3244 02:34:10,728 --> 02:34:11,629 INFRASTRUCTURE AND EXPERTISE FOR 3245 02:34:11,629 --> 02:34:13,698 PUBLIC-PRIVATE PARTNERSHIPS AND 3246 02:34:13,698 --> 02:34:17,268 THIS IS RELATED A LITTLE BIT TO 3247 02:34:17,268 --> 02:34:20,338 WHAT WE HEARD DISCUSSING ABOUT 3248 02:34:20,338 --> 02:34:24,208 THE NUCLEATED ROLE OF THE 3249 02:34:24,208 --> 02:34:25,643 FREDERICK NATIONAL LAB FOR 3250 02:34:25,643 --> 02:34:27,578 MULTIPLE USES FOR COVID-19 AS WE 3251 02:34:27,578 --> 02:34:29,414 AND SEE WITH RESULTS FROM CDC 3252 02:34:29,414 --> 02:34:32,216 AND W.H.O., THE INFECTIONS ARE 3253 02:34:32,216 --> 02:34:34,719 GOING UP. 3254 02:34:34,719 --> 02:34:39,023 THIS COVID-19 IS REALLY ONE OF 3255 02:34:39,023 --> 02:34:40,591 THE TOP CAUSES OF DEATH IN 3256 02:34:40,591 --> 02:34:46,597 CANCER PATIENTS SO WE NEED TO DO 3257 02:34:46,597 --> 02:34:53,805 A LOT OF RESEARCH WITH COVID-19 3258 02:34:53,805 --> 02:34:54,672 BECAUSE IT'S HERE AND HERE TO 3259 02:34:54,672 --> 02:34:57,942 STAY FOR A WHILE AND CAN AFFECT 3260 02:34:57,942 --> 02:35:01,012 VULNERABLE POPULATIONS SUCH AS 3261 02:35:01,012 --> 02:35:02,213 PEOPLE LIVING WITH CANCER 3262 02:35:02,213 --> 02:35:03,581 UTILIZING AGAIN THE PLUG AND 3263 02:35:03,581 --> 02:35:06,317 PLAY TECHNOLOGIES WE HAVE AND 3264 02:35:06,317 --> 02:35:09,354 ALL THE INFRASTRUCTURE AND WE'RE 3265 02:35:09,354 --> 02:35:11,155 INTERESTED IN CANCER VACCINE 3266 02:35:11,155 --> 02:35:13,358 IMMUNOLOGY AND STANDARDS 3267 02:35:13,358 --> 02:35:14,359 DEVELOPMENT AND THE THIS COULD 3268 02:35:14,359 --> 02:35:16,427 BE ANOTHER MODEL FOR APPLICATION 3269 02:35:16,427 --> 02:35:18,730 BEYOND COVID-19. 3270 02:35:18,730 --> 02:35:21,332 I WANT TO THANK EVERYONE THAT 3271 02:35:21,332 --> 02:35:22,266 MADE THIS POSSIBLE. 3272 02:35:22,266 --> 02:35:24,902 IT WAS REALLY AN AMAZING 3273 02:35:24,902 --> 02:35:25,503 COLLABORATION. 3274 02:35:25,503 --> 02:35:28,773 I HAVE TO GIVE A SPECIAL THANKS 3275 02:35:28,773 --> 02:35:33,711 TO DR. LOWEY SINCE HE WAS WITH 3276 02:35:33,711 --> 02:35:37,815 US SINCE THE FIRST DAY -- 3277 02:35:37,815 --> 02:35:43,254 DR. LOWY AND ALL THE COLLEAGUES 3278 02:35:43,254 --> 02:35:45,656 AT NCI. 3279 02:35:45,656 --> 02:35:47,025 AND JIM CHERRY WAS INSTRUMENTAL 3280 02:35:47,025 --> 02:35:50,328 AT THE BEGINNING AND EVERYONE AT 3281 02:35:50,328 --> 02:35:52,897 THE FREDERICK NATIONAL LAB AND 3282 02:35:52,897 --> 02:35:54,565 THE LABORATORY WORKED TIRELESSLY 3283 02:35:54,565 --> 02:35:57,235 DURING THE PANDEMIC AND IT WAS A 3284 02:35:57,235 --> 02:36:02,707 JOY TO WORK WITH THE FDA AND CDC 3285 02:36:02,707 --> 02:36:12,650 AND W.H.O. AND MY COLLEAGUES AND 3286 02:36:12,650 --> 02:36:14,452 THE BILL AND MELINDA GATES 3287 02:36:14,452 --> 02:36:17,722 FOUNDATION AND THANK YOU FOR 3288 02:36:17,722 --> 02:36:19,257 LISTENING AROUND HAPPY TO ANSWER 3289 02:36:19,257 --> 02:36:19,524 QUESTIONS. 3290 02:36:19,524 --> 02:36:20,024 >> THANK YOU. 3291 02:36:20,024 --> 02:36:23,194 TWO OUTSTANDING PRESENTATIONS. 3292 02:36:23,194 --> 02:36:25,663 WE HAVE A MINUTE OR TWO FOR 3293 02:36:25,663 --> 02:36:25,930 QUESTIONS. 3294 02:36:25,930 --> 02:36:35,339 ALLISON. 3295 02:36:35,339 --> 02:36:36,407 >> CAN YOU HEAR ME? 3296 02:36:36,407 --> 02:36:37,308 >> YES. 3297 02:36:37,308 --> 02:36:39,377 >> I UNMUTED MYSELF. 3298 02:36:39,377 --> 02:36:40,645 OUTSTANDING. 3299 02:36:40,645 --> 02:36:42,513 THIS IS JUST AWESOME. 3300 02:36:42,513 --> 02:36:43,714 DR. RATHMELL AT THE BEGINNING 3301 02:36:43,714 --> 02:36:46,684 WAS SAYING WHAT CAN WE DO FOR 3302 02:36:46,684 --> 02:36:51,122 THE FUTURE OF IF FNL. 3303 02:36:51,122 --> 02:36:52,323 THIS EFFORT SERONET'S EFFORT IS 3304 02:36:52,323 --> 02:36:53,891 A POSTER CHILD OF THAT FUTURE. 3305 02:36:53,891 --> 02:36:55,326 YOU'RE INTERACTING WITH OTHER 3306 02:36:55,326 --> 02:37:01,532 AGENCIES TO HELP THEM DO THEIR 3307 02:37:01,532 --> 02:37:01,699 JOB. 3308 02:37:01,699 --> 02:37:05,269 YOU'RE LEADING OUR UNDERSTANDING 3309 02:37:05,269 --> 02:37:06,704 OF THESE ON VULNERABLE 3310 02:37:06,704 --> 02:37:10,708 POPULATIONS. 3311 02:37:10,708 --> 02:37:18,683 I THINK IT'S JUST AN A COMMENT 3312 02:37:18,683 --> 02:37:23,621 OF SAYING THIS TYPE OF RESOURCE 3313 02:37:23,621 --> 02:37:24,922 REPRESENTS WHAT A NATIONAL LAB 3314 02:37:24,922 --> 02:37:25,790 SHOULD BE PUTTING FORWARD. 3315 02:37:25,790 --> 02:37:32,630 ALL THE PARTNERSHIPS, PUBLIC, 3316 02:37:32,630 --> 02:37:38,469 PRIVATE, OTHER ORGANIZATIONS OR 3317 02:37:38,469 --> 02:37:39,504 CONGRATULATIONS ON A JOB WELL 3318 02:37:39,504 --> 02:37:39,704 DONE. 3319 02:37:39,704 --> 02:37:46,344 ARE THIS EM PEOPLE IN YOUR 3320 02:37:46,344 --> 02:37:53,851 GROUP PUBLISHING TO DISSEMINATE 3321 02:37:53,851 --> 02:37:56,821 THE RESEARCH BECAUSE THERE'S A 3322 02:37:56,821 --> 02:37:58,856 DARK OF PUBLICATIONS IN THIS 3323 02:37:58,856 --> 02:38:01,559 AREA TO HELP PEOPLE MOVE TOWARDS 3324 02:38:01,559 --> 02:38:02,760 THIS STANDARDIZATION IN TERMS OF 3325 02:38:02,760 --> 02:38:11,269 COLLECTION PROCESSING, ETCETERA. 3326 02:38:11,269 --> 02:38:12,370 >> WE ARE EXTREMELY EXCITED 3327 02:38:12,370 --> 02:38:13,871 ABOUT THE WORK WE ARE DOING IN 3328 02:38:13,871 --> 02:38:17,141 THIS AREA AND YOUR IDEAS IS 3329 02:38:17,141 --> 02:38:17,341 GREAT. 3330 02:38:17,341 --> 02:38:19,877 WE HAVE BEEN TRYING TO PUBLISH 3331 02:38:19,877 --> 02:38:21,779 METHOD DEVELOPMENT PAPERS. 3332 02:38:21,779 --> 02:38:24,849 WE ALSO PUT IN OUR WEBSITE ALL 3333 02:38:24,849 --> 02:38:30,721 THE SOPs AND VALIDATION 3334 02:38:30,721 --> 02:38:32,123 GUIDELI 3335 02:38:32,123 --> 02:38:34,825 GUIDELINES WITH REGULATORY 3336 02:38:34,825 --> 02:38:37,562 STANDARDS AND THE BIO SPECIMEN 3337 02:38:37,562 --> 02:38:39,130 JOURNALS ARE WONDERFUL. 3338 02:38:39,130 --> 02:38:40,731 THANK YOU VERY MUCH. 3339 02:38:40,731 --> 02:38:41,432 WE'LL CONSIDER. 3340 02:38:41,432 --> 02:38:46,337 >> DR. ROBERTSON. 3341 02:38:46,337 --> 02:38:46,704 >> 3342 02:38:46,704 --> 02:38:48,072 >> GREAT PRESENTATION AND 3343 02:38:48,072 --> 02:38:49,040 IMPRESSIVE WORK. 3344 02:38:49,040 --> 02:38:54,779 I HAVE A QUESTION ON WHAT YOU 3345 02:38:54,779 --> 02:38:58,316 MAY HAVE UNDERSTOOD BASED ON 3346 02:38:58,316 --> 02:39:03,854 WHAT'S OUT NOW IN THE CONTEXT OF 3347 02:39:03,854 --> 02:39:10,628 LONG COVID AND AND INCIDENTS OF 3348 02:39:10,628 --> 02:39:10,861 CANCER. 3349 02:39:10,861 --> 02:39:12,997 DO THEY HAVE MORE INCIDENTS OF 3350 02:39:12,997 --> 02:39:13,297 LONG COVID? 3351 02:39:13,297 --> 02:39:15,700 I THINK SOME STUDIES HAVE SHOWN 3352 02:39:15,700 --> 02:39:17,101 THAT BUT I'M CONCERNED WE NEED 3353 02:39:17,101 --> 02:39:22,607 TO START LOOKING AT OTHER 3354 02:39:22,607 --> 02:39:26,110 POTENTIAL CANCERS THAT ARE HPV 3355 02:39:26,110 --> 02:39:33,451 RELATED CANCERS AND EPSTEIN-BARR 3356 02:39:33,451 --> 02:39:35,853 VIRUS THAT THRIVE MALIGNANCIES. 3357 02:39:35,853 --> 02:39:37,421 THESE TYPES OF CANCERS MIGHT 3358 02:39:37,421 --> 02:39:41,225 HAVE A GREATER INCREASE 3359 02:39:41,225 --> 02:39:42,526 INCIDENTS IN PATIENTS THAT HAVE 3360 02:39:42,526 --> 02:39:43,361 LONG COVID. 3361 02:39:43,361 --> 02:39:46,364 DO WE HAVE ANY DATA OR 3362 02:39:46,364 --> 02:39:48,499 INFORMATION AS TO WHAT MIGHT BE 3363 02:39:48,499 --> 02:39:59,010 HAPPENING IN THESE POPULATIONS? 3364 02:39:59,010 --> 02:40:00,811 >> A NUMBER OF INVESTIGATORS ARE 3365 02:40:00,811 --> 02:40:02,413 BEGINNING TO LOOK AT THIS 3366 02:40:02,413 --> 02:40:05,182 QUESTION AND LOOK AT THE 3367 02:40:05,182 --> 02:40:05,950 CORRELATION BETWEEN LONG COVID 3368 02:40:05,950 --> 02:40:06,317 AND CANCER. 3369 02:40:06,317 --> 02:40:12,490 I KNOW THERE'S BEEN A NUMBER OF 3370 02:40:12,490 --> 02:40:21,999 ARTICLES IN TERMS OF A 3371 02:40:21,999 --> 02:40:23,934 DEFINITIVE STATEMENT AND IN 3372 02:40:23,934 --> 02:40:26,604 TERMS OF HPV AND VIRUSES I DON'T 3373 02:40:26,604 --> 02:40:29,940 KNOW WE HAVE ENOUGH DATA TO BE 3374 02:40:29,940 --> 02:40:30,975 DEFINITIVE BUT IT'S AN IMPORTANT 3375 02:40:30,975 --> 02:40:33,744 AREA PEOPLE ARE LOOKING AT 3376 02:40:33,744 --> 02:40:34,712 ESPECIALLY THE RELATIONSHIP 3377 02:40:34,712 --> 02:40:35,846 BETWEEN THE VIRUS ITSELF AND 3378 02:40:35,846 --> 02:40:41,952 CANCER. 3379 02:40:41,952 --> 02:40:44,322 >> I AGREE WITH DR. SINGER. 3380 02:40:44,322 --> 02:40:45,056 DEFINITELY THERE ARE SEVERAL 3381 02:40:45,056 --> 02:40:48,292 PAPERS IN THIS AREA. 3382 02:40:48,292 --> 02:40:49,994 THERE'S INDICATION THAT 3383 02:40:49,994 --> 02:40:53,297 INCIDENTS OF LONG COVID IS 3384 02:40:53,297 --> 02:40:55,366 HIGHER IN IMMUNOCOMPROMISED 3385 02:40:55,366 --> 02:40:56,167 INDIVIDUALS BUT WE NEED MORE 3386 02:40:56,167 --> 02:40:56,367 DATA. 3387 02:40:56,367 --> 02:41:03,274 I THINK ONE OF THE GOALS OF THE 3388 02:41:03,274 --> 02:41:05,710 REAL WORLD INFRASTRUCTURE THAT 3389 02:41:05,710 --> 02:41:09,613 IS BEING LED AND MORE THAN $5 3390 02:41:09,613 --> 02:41:13,084 MILLION PATIENTS INCLUDED IN 3391 02:41:13,084 --> 02:41:19,290 THAT DATABASE I THINK 1.3 3392 02:41:19,290 --> 02:41:21,058 MILLION CANCER PATIENTS IT WILL 3393 02:41:21,058 --> 02:41:23,394 BE EXCELLENT TO LOOK AT THE 3394 02:41:23,394 --> 02:41:28,099 CANCER PATIENTS AND LOOK AT THE 3395 02:41:28,099 --> 02:41:29,133 INFRASTRUCTURE. 3396 02:41:29,133 --> 02:41:31,135 THIS IS WHY IT'S IMPORTANT TO 3397 02:41:31,135 --> 02:41:33,270 LOOK AT INFRASTRUCTURE TO ANSWER 3398 02:41:33,270 --> 02:41:34,705 QUICKLY THESE TYPES OF 3399 02:41:34,705 --> 02:41:37,341 QUESTIONS. 3400 02:41:37,341 --> 02:41:39,443 >> IT'S AFTER 4:00 PUT WE HAVE 3401 02:41:39,443 --> 02:41:42,646 ONE MORE QUESTION. 3402 02:41:42,646 --> 02:41:43,547 >> THANK YOU. 3403 02:41:43,547 --> 02:41:46,650 I WAS GOING TO ASK ABOUT LONG 3404 02:41:46,650 --> 02:41:48,018 COVID BUT MORE SPECIFICALLY CAN 3405 02:41:48,018 --> 02:41:50,388 YOU SPEAK TO WHAT, IF ANY, 3406 02:41:50,388 --> 02:41:53,824 COLLABORATIONS ARE ONGOING WITH 3407 02:41:53,824 --> 02:41:55,960 THE RECOVER INITIATIVE 3408 02:41:55,960 --> 02:41:58,562 SPECIFICALLY FOCUSSED ON LONG 3409 02:41:58,562 --> 02:42:00,030 COVID AND I GUESS I'LL GO BACK 3410 02:42:00,030 --> 02:42:02,299 TO THE QUESTION PREVIOUSLY ASKED 3411 02:42:02,299 --> 02:42:05,770 ABOUT DATA AND WHAT ARE THE 3412 02:42:05,770 --> 02:42:08,839 ACTIVITIES ON TRYING TO MAKE 3413 02:42:08,839 --> 02:42:09,774 THIS DATA AVAILABLE AND USED BY 3414 02:42:09,774 --> 02:42:15,279 THE RESEARCH COMMUNITY. 3415 02:42:15,279 --> 02:42:20,317 >> IN TERMS OF RECOVER, WE DON'T 3416 02:42:20,317 --> 02:42:23,888 HAVE A FORMAL COLLABORATION WITH 3417 02:42:23,888 --> 02:42:25,022 RECOVER THOUGH OUR NCI STAFF IS 3418 02:42:25,022 --> 02:42:26,457 IN COMMUNICATION WITH THE 3419 02:42:26,457 --> 02:42:26,991 RECOVER STAFF IN SHARING 3420 02:42:26,991 --> 02:42:33,764 INFORMATION. 3421 02:42:33,764 --> 02:42:35,332 IN TERMS OF THE DATA SHARING 3422 02:42:35,332 --> 02:42:37,535 THAT'S A REQUIREMENT OF SERONET 3423 02:42:37,535 --> 02:42:40,504 ALL THE DATA BE MADE PUBLICALLY 3424 02:42:40,504 --> 02:42:42,573 AVAILABLE IMMEDIATELY UPON 3425 02:42:42,573 --> 02:42:42,873 PUBLICATION. 3426 02:42:42,873 --> 02:42:44,008 THE COORDINATING CENTER REALLY 3427 02:42:44,008 --> 02:42:46,710 IS RESPONSIBLE FOR THAT. 3428 02:42:46,710 --> 02:42:50,214 THEY'VE BEEN DOING A GREAT JOB. 3429 02:42:50,214 --> 02:42:52,483 DO YOU WANT TO COMMENT? 3430 02:42:52,483 --> 02:42:56,320 >> ALL THE DATA, 413 3431 02:42:56,320 --> 02:42:57,922 PUBLICATIONS FROM SERONET IS 3432 02:42:57,922 --> 02:43:02,092 DEPOSITED IN IMPORT SO WE HAVE A 3433 02:43:02,092 --> 02:43:07,932 COLLABORATION WITH NIAID FOR 3434 02:43:07,932 --> 02:43:11,769 THAT CURATION AND SPEND HERE WE 3435 02:43:11,769 --> 02:43:17,274 MADE THE DATA AVAILABLE TO ALL 3436 02:43:17,274 --> 02:43:19,109 SERONET INVESTIGATORS. 3437 02:43:19,109 --> 02:43:20,611 WITHIN OUR CENTER FOR SEROLOGY 3438 02:43:20,611 --> 02:43:23,581 AND ACADEMIC PREPAREDNESS WE'RE 3439 02:43:23,581 --> 02:43:28,252 DEVELOPING A COMPREHENSIVE DATA 3440 02:43:28,252 --> 02:43:34,725 RESOURCE AND WE ARE MAKING A 3441 02:43:34,725 --> 02:43:37,027 DATE PLANNING TO MAKE IT 3442 02:43:37,027 --> 02:43:38,696 AVAILABLE TO THE OUTSIDE. 3443 02:43:38,696 --> 02:43:44,902 >> RODNEY HAS HIS HAND UP. 3444 02:43:44,902 --> 02:43:48,839 SORRY, HOPEFULLY IT'S A QUICK 3445 02:43:48,839 --> 02:43:49,974 QUESTION BECAUSE IT'S AFTER 3446 02:43:49,974 --> 02:43:50,708 4:00. 3447 02:43:50,708 --> 02:43:51,542 YOU'RE MUTED. 3448 02:43:51,542 --> 02:43:52,843 >> THANK YOU. 3449 02:43:52,843 --> 02:43:54,345 KIND OF LATE BUT I THINK THIS IS 3450 02:43:54,345 --> 02:43:59,950 EXACTLY WHAT WE HAVE BEEN ABLE 3451 02:43:59,950 --> 02:44:01,452 TO ORGANIZE PUBLIC-PRIVATE 3452 02:44:01,452 --> 02:44:03,821 PARTNERSHIPS TO EXPAND ON THE 3453 02:44:03,821 --> 02:44:05,489 DETAIL OF SEROLOGY. 3454 02:44:05,489 --> 02:44:08,926 FOR A LONG TIME PEOPLE THOUGHT 3455 02:44:08,926 --> 02:44:10,728 ABOUT THE RESPONSE AND DO YOU 3456 02:44:10,728 --> 02:44:12,796 MEASURE IT AND CROSS OVER AND 3457 02:44:12,796 --> 02:44:15,099 THIS IS IMPORTANT. 3458 02:44:15,099 --> 02:44:22,640 AND THEN HAVING A TOOL NOW 3459 02:44:22,640 --> 02:44:24,475 AVAILABLE FOR TREATMENT AND 3460 02:44:24,475 --> 02:44:24,808 DEVELOPMENT. 3461 02:44:24,808 --> 02:44:29,146 THE QUESTION I HAVE IS ALL THE 3462 02:44:29,146 --> 02:44:34,118 DATA THAT YOU COLLECTED ARE 3463 02:44:34,118 --> 02:44:37,655 MULTI-FACETED RESPONSE AND OTHER 3464 02:44:37,655 --> 02:44:45,996 THINGS SO HOW DO YOU THINK THIS 3465 02:44:45,996 --> 02:44:47,798 REPOSITORY WILL BE USED AND 3466 02:44:47,798 --> 02:44:49,099 ACCESSED BY INVESTIGATORS USING 3467 02:44:49,099 --> 02:44:52,102 THE POOL OF SAMPLES TO ANALYZE 3468 02:44:52,102 --> 02:44:53,737 CLINICAL DATA, BIG DATA, THE 3469 02:44:53,737 --> 02:44:59,877 DATA THAT EXISTS AND TRYING TO 3470 02:44:59,877 --> 02:45:01,912 UNDERSTAND AND TAKE ARE LEADS TO 3471 02:45:01,912 --> 02:45:04,448 NEXT GEN OF VACCINE DEVELOPMENT 3472 02:45:04,448 --> 02:45:06,050 POTENTIALLY FOR CANCER VACCINE 3473 02:45:06,050 --> 02:45:08,519 AND WHAT ARE THE STRATEGIES 3474 02:45:08,519 --> 02:45:10,721 BECAUSE WE ALREADY EXPANDED A 3475 02:45:10,721 --> 02:45:15,192 LOT. 3476 02:45:15,192 --> 02:45:18,395 AT LEAST WHAT ARE THE TOOL SETS 3477 02:45:18,395 --> 02:45:23,133 CDC MAY NOT HAVE BUT YOU HAVE 3478 02:45:23,133 --> 02:45:23,767 ORGANIZED? 3479 02:45:23,767 --> 02:45:25,836 SO LESSONS LEARNED CAN BE 3480 02:45:25,836 --> 02:45:29,039 APPLIED TO MULTIPLE DISEASES AND 3481 02:45:29,039 --> 02:45:32,610 SOME INCLUDE PEOPLE WITH LUPUS 3482 02:45:32,610 --> 02:45:35,045 HAVE IMMUNE RESPONSES THAT MAY 3483 02:45:35,045 --> 02:45:36,914 NOT RESPOND TO COVID FOR EXAMPLE 3484 02:45:36,914 --> 02:45:40,084 AND THAT COULD BE A FUNDAMENTAL 3485 02:45:40,084 --> 02:45:40,918 UNDERSTANDING THAT I THINK WE'RE 3486 02:45:40,918 --> 02:45:44,021 IN A POSITION TO HELP. 3487 02:45:44,021 --> 02:45:49,026 >> SO, IN TERMS OF THE BIO 3488 02:45:49,026 --> 02:45:50,194 SPECIMENS THAT WERE ORIGINALLY 3489 02:45:50,194 --> 02:45:55,599 COLLECTED BOTH FOR THE SEROLOGY 3490 02:45:55,599 --> 02:45:58,569 LAB AND IT FOR THE SERONET 3491 02:45:58,569 --> 02:45:59,570 INVESTIGATORS BUT NOW THAT WE'RE 3492 02:45:59,570 --> 02:46:01,672 COMING TO THE END OF SERONET 3493 02:46:01,672 --> 02:46:06,577 WE'LL BE MAKING THE BIO 3494 02:46:06,577 --> 02:46:07,211 SPECIMENS STANDARDS AVAILABLE TO 3495 02:46:07,211 --> 02:46:10,114 THE GENERAL COMMUNITY. 3496 02:46:10,114 --> 02:46:16,720 PEOPLE INTERESTED IN THAT SHOULD 3497 02:46:16,720 --> 02:46:19,423 LET US KNOW ALICIA DO YOU WANT 3498 02:46:19,423 --> 02:46:20,357 TO RESPOND TO THE REST OF THE 3499 02:46:20,357 --> 02:46:20,624 QUESTION. 3500 02:46:20,624 --> 02:46:23,827 >> I THINK IT'S A GOLD MINE OF 3501 02:46:23,827 --> 02:46:25,129 SPECIMENS AND OUR GOAL AS 3502 02:46:25,129 --> 02:46:26,430 DR. SINGER WAS SAYING IS MAKING 3503 02:46:26,430 --> 02:46:29,500 IT AVAILABLE TO THE OUTSIDE. 3504 02:46:29,500 --> 02:46:31,802 WE HAVE BEEN IN COMMUNICATIONS 3505 02:46:31,802 --> 02:46:32,936 CREATING A COMMUNICATION PLAN TO 3506 02:46:32,936 --> 02:46:35,739 MAKE THAT HAPPEN IN THE UPCOMING 3507 02:46:35,739 --> 02:46:38,042 FEW MONTHS SO THAT'S REALLY 3508 02:46:38,042 --> 02:46:40,678 WONDERFUL AND THEN IN TERMS OF 3509 02:46:40,678 --> 02:46:43,414 EVEN UTILIZING FOR OTHER 3510 02:46:43,414 --> 02:46:45,683 TECHNOLOGIES AND REALLY FOR 3511 02:46:45,683 --> 02:46:49,053 ADVANCING SCIENCE AND HYPOTHESIS 3512 02:46:49,053 --> 02:46:52,823 GENERATING, WE HAVE A STUDY WE 3513 02:46:52,823 --> 02:46:54,625 JUST DID USING THE TECHNOLOGY 3514 02:46:54,625 --> 02:46:57,027 FOR PROTEOMICS TO SIGH IF WE CAN 3515 02:46:57,027 --> 02:47:02,066 COME UP WITH SOME MARKERS 3516 02:47:02,066 --> 02:47:04,535 PREDICTIVE OF FAILURE OR SUCCESS 3517 02:47:04,535 --> 02:47:08,105 TO VACCINATION AND WE ARE 3518 02:47:08,105 --> 02:47:10,708 ANALYZING AND SUBMITTING THE 3519 02:47:10,708 --> 02:47:11,909 MANUSCRIPT NOW BUT THERE WILL BE 3520 02:47:11,909 --> 02:47:14,078 OPPORTUNITIES FOR USING PDMCs 3521 02:47:14,078 --> 02:47:18,716 FOR GENERATION OF MONOCLONAL 3522 02:47:18,716 --> 02:47:22,086 ANTIBODIES AND THERE COULD BE 3523 02:47:22,086 --> 02:47:24,188 UTILIZATION OF DIFFERENT 3524 02:47:24,188 --> 02:47:24,521 TECHNOLOGIES. 3525 02:47:24,521 --> 02:47:26,724 I THINK THIS WILL BE WONDERFUL 3526 02:47:26,724 --> 02:47:27,524 TO UTILIZE. 3527 02:47:27,524 --> 02:47:29,493 AGAIN, WE HAVE SPECIMENS FROM 3528 02:47:29,493 --> 02:47:31,028 PHASES THAT WE'LL NEVER HAVE 3529 02:47:31,028 --> 02:47:36,166 AGAIN. 3530 02:47:36,166 --> 02:47:37,835 EARLY ON IN THE PANDEMIC 3531 02:47:37,835 --> 02:47:38,736 INFECTED INDIVIDUALS AND 3532 02:47:38,736 --> 02:47:40,437 INDIVIDUALS WITH DIFFERENT 3533 02:47:40,437 --> 02:47:45,142 VACCINES THAT WERE APPROVED AND 3534 02:47:45,142 --> 02:47:51,048 DIFFERENT TIMES OF THE MONOAND 3535 02:47:51,048 --> 02:47:51,315 BIVALENT. 3536 02:47:51,315 --> 02:47:53,884 IT'S WHAT WE PLAN TO LEVERAGE. 3537 02:47:53,884 --> 02:47:58,722 >> I WAS THINKING AN ORGANIZED 3538 02:47:58,722 --> 02:48:00,791 WAY TO MANAGE AND HELP 3539 02:48:00,791 --> 02:48:02,092 FACILITATE THAT OPPOSED TO ONE 3540 02:48:02,092 --> 02:48:02,559 OFF. 3541 02:48:02,559 --> 02:48:04,695 THAT WOULD BE HELPFUL. 3542 02:48:04,695 --> 02:48:05,996 >> THAT'S AN EXCELLENT 3543 02:48:05,996 --> 02:48:06,697 SUGGESTION. 3544 02:48:06,697 --> 02:48:09,399 I THINK SOMETHING WE'LL TALK 3545 02:48:09,399 --> 02:48:12,336 ABOUT HOW DO WE HAVE A 3546 02:48:12,336 --> 02:48:13,003 COORDINATED EFFORT BEYOND 3547 02:48:13,003 --> 02:48:13,403 SERONET. 3548 02:48:13,403 --> 02:48:13,971 >> THANK YOU. 3549 02:48:13,971 --> 02:48:16,039 >> THANKS VERY MUCH. 3550 02:48:16,039 --> 02:48:18,375 I'M SORRY AS CHAIR I ALWAYS TRY 3551 02:48:18,375 --> 02:48:20,144 TO BE PROMPT AND IT'S ALMOST 10 3552 02:48:20,144 --> 02:48:22,713 MINUTES AFTER 4:00 BUT I THINK 3553 02:48:22,713 --> 02:48:26,750 IT WAS WORTH IT BECAUSE THESE 3554 02:48:26,750 --> 02:48:30,120 WERE INTRIGUING PRESENTATIONS 3555 02:48:30,120 --> 02:48:31,755 GENERATED A LOT OF INTEREST. 3556 02:48:31,755 --> 02:48:34,691 EVERY TIME WE HEAR ABOUT THIS IT 3557 02:48:34,691 --> 02:48:35,125 GENERATES INTEREST. 3558 02:48:35,125 --> 02:48:36,260 THANK YOU VERY MUCH. 3559 02:48:36,260 --> 02:48:36,894 REALLY OUTSTANDING. 3560 02:48:36,894 --> 02:48:42,065 I THINK WE'RE AT THE END OF OUR 3561 02:48:42,065 --> 02:48:42,299 AGENDA. 3562 02:48:42,299 --> 02:48:48,872 CAN I HAVE A MOTION TO ADJOURN? 3563 02:48:48,872 --> 02:48:51,775 >> SECOND? 3564 02:48:51,775 --> 02:48:53,210 ALL IN FAVOR. 3565 02:48:53,210 --> 02:48:54,011 THANK YOU VERY MUCH EVERYBODY. 3566 02:48:54,011 --> 02:48:57,481 THANK YOU ALL FOR JOINING US AND 3567 02:48:57,481 --> 02:48:59,116 FOR THE WONDERFUL CONVERSATION 3568 02:48:59,116 --> 02:49:02,152 AND HOPEFULLY WE'LL ALL SEE EACH 3569 02:49:02,152 --> 02:49:02,886 OTHER AT OUR NEXT MEETING. 3570 02:49:02,886 --> 02:49:13,130 >> THANK YOU.