WEBVTT 1 00:00:00.280 --> 00:00:03.960 Welcome to Farmer Talk Radio. This podcast is focused on 2 00:00:04.200 --> 00:00:08.960 enhand strategic FDA collaboration working with Cedar and Sieber from 3 00:00:08.960 --> 00:00:12.000 the twenty twenty five Chief Medical Officer Summit three sixty. 4 00:00:12.279 --> 00:00:16.640 For more information on the CMO Summit, editorials, podcasts, or webcasts, 5 00:00:16.920 --> 00:00:19.839 please visit CMO three sixty dot org. Thank you and 6 00:00:19.920 --> 00:00:22.239 enjoy the podcast. We have. 7 00:00:23.879 --> 00:00:28.280 A group of panelists with a very diverse experience of 8 00:00:28.760 --> 00:00:34.000 regulatory interactions and essentially get their advice on the best 9 00:00:34.039 --> 00:00:40.000 ways of working with Cedar and Seber. Inevitably, with all 10 00:00:40.039 --> 00:00:43.520 of the changes that are happening in the FDA, we 11 00:00:43.600 --> 00:00:46.880 may have to address some of those potential changes. But 12 00:00:47.159 --> 00:00:50.920 the focus here is really on people's experience of how 13 00:00:50.960 --> 00:00:53.920 best to interact with the FDA that we know and love. 14 00:00:54.320 --> 00:00:56.840 So with that, I'm going to ask for introductions. 15 00:00:57.079 --> 00:00:57.600 I'll start off. 16 00:00:57.640 --> 00:00:59.840 I'm Peter Francis. I'm the Chief Medical Officer in chief 17 00:01:00.000 --> 00:01:05.159 antipic Officer at Rath Therapeutics, which is an aav gene 18 00:01:05.159 --> 00:01:10.400 therapy company principally working in the ophthalmic space. I have 19 00:01:10.560 --> 00:01:15.879 a considerable amount of experience of translating into early phase development. 20 00:01:16.120 --> 00:01:22.239 Number of indication number of products for principally rare diseases 21 00:01:22.359 --> 00:01:27.879 in the ophthalmology and other areas. 22 00:01:28.719 --> 00:01:31.719 Richard Granton, chief medical Officer Lyndrith Therapeutics were an oral 23 00:01:31.799 --> 00:01:34.760 drug delivery technology out of MIT, but prior to that, 24 00:01:34.879 --> 00:01:38.519 I worked in the pain space in well and carometabolic. 25 00:01:39.040 --> 00:01:40.120 Cart preaching. 26 00:01:43.239 --> 00:01:46.280 Our preaching Chief medical officer at Precision for Medicine. We're 27 00:01:46.319 --> 00:01:51.280 a global cro focused on oncology and rare disease. Prior 28 00:01:51.319 --> 00:01:54.120 to my role at Precision, I joined in May of 29 00:01:54.200 --> 00:01:57.519 last year. I was at the FDA for nearly ten years. 30 00:01:57.560 --> 00:01:59.840 In the latter half I served as a division director 31 00:02:00.400 --> 00:02:03.799 of one of the solid tumor oncology divisions within THEEDAR. 32 00:02:05.920 --> 00:02:12.159 I'm Norman Sussman. I'm chief medical Officer at Direct. My 33 00:02:12.280 --> 00:02:16.039 training is in liver disease and the company is focused 34 00:02:16.080 --> 00:02:22.159 on an acute form of alcohol liver disease called alcohol 35 00:02:22.280 --> 00:02:23.680 associated hipatitis. 36 00:02:25.719 --> 00:02:28.360 That's great, thanks for the introductions. 37 00:02:30.080 --> 00:02:32.759 We thought the first area that we might focus on 38 00:02:33.240 --> 00:02:35.639 from a sort of best practice is how best to 39 00:02:35.719 --> 00:02:41.639 structure your interactions with the FDA. Examples being how to 40 00:02:41.680 --> 00:02:44.639 prepare who to send and so on. So maybe for 41 00:02:44.719 --> 00:02:47.719 this first question, I'll hand it to Harpreet first, she's 42 00:02:47.719 --> 00:02:49.879 had the most hands on experience at the FDA, and 43 00:02:49.919 --> 00:02:53.479 then we'll get the other panelists to comment to Thanks. 44 00:02:53.719 --> 00:02:56.560 Peter, Well, we were talking earlier about how much to 45 00:02:56.599 --> 00:02:59.719 go into the recent events at FDA, and I think 46 00:02:59.759 --> 00:03:02.879 this panel would be remiss to not, you know, focus 47 00:03:03.000 --> 00:03:05.800 particularly on Cedar and Seber. So I'm just gonna I 48 00:03:05.919 --> 00:03:08.400 am going to answer your question, but I just want 49 00:03:08.439 --> 00:03:11.680 to spend a few moments talking about what has happened 50 00:03:12.199 --> 00:03:15.159 to my former colleagues at the FDA in the last 51 00:03:15.439 --> 00:03:20.120 several weeks and months. And we have seen and this 52 00:03:20.199 --> 00:03:22.360 is two prongs. We'll start with Segur and then moved 53 00:03:22.400 --> 00:03:28.319 to Sieber. C Derr has seen substantial departures from Peter Stein, 54 00:03:28.400 --> 00:03:31.400 who headed the Office of New Drugs, so that crosses 55 00:03:31.879 --> 00:03:36.039 all therapeutic areas. In the oncology group, You've seen the 56 00:03:36.039 --> 00:03:39.759 departures of key leaders in the Oncology Center of Excellence 57 00:03:41.000 --> 00:03:47.159 with Mark there, Paul Klutz, the head CEDAR head, Patricia 58 00:03:47.199 --> 00:03:50.400 Cavezoni now CMO at Pfizer. So that predated some of 59 00:03:50.439 --> 00:03:53.800 this of what we saw in the last couple of weeks. 60 00:03:54.599 --> 00:03:58.879 And I think as far as interacting with FDA. What 61 00:03:59.000 --> 00:04:03.400 you will see there is as far as Sea dur. 62 00:04:03.400 --> 00:04:05.560 Goes, I think things will be. 63 00:04:05.400 --> 00:04:10.879 Somewhat routine and normal in terms of I and D reviews, meetings. 64 00:04:10.919 --> 00:04:12.520 They're continuing to have them. 65 00:04:13.000 --> 00:04:16.040 What I do think we need to pay special attention 66 00:04:16.160 --> 00:04:19.160 to is who's showing up at those meetings, who's doing 67 00:04:19.199 --> 00:04:23.680 the talking, who's noticeably absent, because more departures will come, 68 00:04:23.800 --> 00:04:29.519 so those noticeably absent leaders may be actually recused because 69 00:04:29.519 --> 00:04:33.839 they're looking elsewhere. But I think these also present opportunities 70 00:04:33.959 --> 00:04:38.360 for emerging leaders to come through and take acting positions 71 00:04:38.519 --> 00:04:44.279 as acting associate directors, deputy directors, and so forth. With Oncology, 72 00:04:44.600 --> 00:04:47.920 who makes up about forty percent of sedar's work, I 73 00:04:48.000 --> 00:04:52.759 do think they do have good leadership remaining, and so 74 00:04:53.360 --> 00:04:55.360 we'll get later into the panel about what I think 75 00:04:55.519 --> 00:04:57.240 those strategic interactions should look like. 76 00:04:57.879 --> 00:04:58.360 See Burr. 77 00:04:58.480 --> 00:05:01.079 On the other hand, I think I saw a very 78 00:05:01.160 --> 00:05:06.600 substantial loss with Peter Marx, who was really presiding not 79 00:05:06.639 --> 00:05:09.480 only over all the vaccine work, but this very robust 80 00:05:10.000 --> 00:05:15.160 cell engene development area, really setting up those regulatory frameworks 81 00:05:15.199 --> 00:05:19.319 for the first Crisper approval with CASHJEV, the first celling 82 00:05:19.360 --> 00:05:24.240 gene approval for pediatric form of leukemia and so not 83 00:05:24.480 --> 00:05:28.279 having him at the HELM I think should cause some 84 00:05:28.360 --> 00:05:31.959 concern and wanting to understand in the months moving forward, 85 00:05:32.279 --> 00:05:36.639 who's going to fill that gap and will those policies 86 00:05:36.720 --> 00:05:39.480 and frameworks that he had been developing to really streamline 87 00:05:39.480 --> 00:05:42.920 and expedite. You know, there's over two thousand cell e 88 00:05:43.000 --> 00:05:46.800 gene products in the pipeline, there's over thirty registrational phase 89 00:05:46.839 --> 00:05:49.399 three trials and cell e gene so Sibur, I think 90 00:05:49.439 --> 00:05:52.720 is where you're going to see a substantial deficit in leadership, 91 00:05:52.759 --> 00:05:54.399 and you know, we need to look to see in 92 00:05:54.439 --> 00:05:56.759 the coming months who's going to step up and fill 93 00:05:56.800 --> 00:06:00.800 those roles all with the other And I'll talk a 94 00:06:00.800 --> 00:06:03.319 little more and then we'll come into how I think 95 00:06:03.360 --> 00:06:05.639 these can be opportunities to enhance our interactions. 96 00:06:05.680 --> 00:06:08.000 But I think you hit on something it's really critical 97 00:06:08.040 --> 00:06:10.600 to the discussion this afternoon. I just want to go 98 00:06:10.720 --> 00:06:13.000 back to, which is I think a lot of us 99 00:06:13.040 --> 00:06:17.680 have realized along the way that the FDA holds the 100 00:06:17.680 --> 00:06:22.399 collective knowledge, if they can't talk about it specifically, are 101 00:06:22.439 --> 00:06:25.040 there any concerns that you have that that collective knowledge 102 00:06:25.079 --> 00:06:27.399 may be may be affected. 103 00:06:26.959 --> 00:06:31.519 By this, absolutely, yes, and I think that going to 104 00:06:31.560 --> 00:06:35.439 the opportunities, I think there are several opportunities for those 105 00:06:35.480 --> 00:06:37.680 of us in this room, and as we're thinking about 106 00:06:37.680 --> 00:06:42.240 building our teams and who we send to the FDA meetings. 107 00:06:42.279 --> 00:06:46.759 You want to as cmos, especially of biotech, you are 108 00:06:46.879 --> 00:06:48.759 the lateral to the division director. 109 00:06:48.800 --> 00:06:50.360 The division directors are mds. 110 00:06:50.879 --> 00:06:54.360 They want to talk to the mds who are developing 111 00:06:54.399 --> 00:06:57.759 the asset, and you as cmos, if you have a 112 00:06:57.920 --> 00:07:01.600 robust track record in interacting with the FDA, the newer 113 00:07:01.680 --> 00:07:05.120 FDA leadership may actually need to hear what the precedent 114 00:07:05.240 --> 00:07:07.600 has been, or you may need to beef up your. 115 00:07:07.480 --> 00:07:10.199 Team with some of these FDA folks. 116 00:07:09.959 --> 00:07:12.759 That are being impacted by the reductions and force to 117 00:07:12.839 --> 00:07:16.240 kind of turn back around that knowledge to support you. So, yes, 118 00:07:16.279 --> 00:07:19.839 it's a concern, and also their opportunities to enhance our 119 00:07:19.920 --> 00:07:22.680 collaborations to bring back some of that knowledge. 120 00:07:23.079 --> 00:07:25.000 Yeah, I was going to say, we had a discussion 121 00:07:25.000 --> 00:07:27.879 before and that resonated really well with me. I've worked 122 00:07:27.879 --> 00:07:30.560 primarily in small biotech and so I don't have the 123 00:07:30.560 --> 00:07:35.759 big farmer experience, but oftentimes we see those mistakes made 124 00:07:35.959 --> 00:07:39.839 you see them as regulators and so regular you know, 125 00:07:39.959 --> 00:07:42.639 maybe your regulatory affairs wants to run the show. I 126 00:07:42.680 --> 00:07:45.560 have found that basically it's down to it's about patient 127 00:07:45.639 --> 00:07:49.240 safety and efficacy, and that's a physician the physician discussion oftentimes, 128 00:07:49.240 --> 00:07:51.639 and you need to present it that way. If there's 129 00:07:51.680 --> 00:07:53.839 going to be a discussion about pharmakinetics, you should have 130 00:07:53.839 --> 00:07:56.160 that individual there. You should really plan those meetings that 131 00:07:56.199 --> 00:07:58.439 you bring your best and brightest and pair them up 132 00:07:58.519 --> 00:07:59.680 with the agency. 133 00:08:00.279 --> 00:08:00.879 And I agree. 134 00:08:00.879 --> 00:08:02.839 I think there's an opportunity now for us to come 135 00:08:02.879 --> 00:08:06.560 in and basically restate the historical perspective for them because 136 00:08:06.560 --> 00:08:08.680 we're on the same page about delivering a drug that's 137 00:08:08.720 --> 00:08:10.879 going to improve the lives of patients, and that's what 138 00:08:10.920 --> 00:08:13.399 they want to hear from us. And that's oftentimes we 139 00:08:13.480 --> 00:08:15.600 make it too much about following the guidelines in a 140 00:08:15.680 --> 00:08:19.160 regulatory procedure, and I think we should. My experience is 141 00:08:19.199 --> 00:08:21.319 that does not help very much of getting your agenda 142 00:08:21.360 --> 00:08:23.560 across now. 143 00:08:23.920 --> 00:08:26.639 And I was very encouraged by what Tuprey said because 144 00:08:28.800 --> 00:08:31.959 it happens that I'm in a section where a lot 145 00:08:32.000 --> 00:08:35.120 of my colleagues work. Even though I try not to 146 00:08:35.159 --> 00:08:39.200 have any x party discussions with them. But I think 147 00:08:39.240 --> 00:08:44.440 it's a mistake. Companies frequently view FDA as the opponent, 148 00:08:45.039 --> 00:08:47.960 and it's much better, especially at the medical level, to 149 00:08:48.039 --> 00:08:52.000 think of them as a collaborator. They first of all, 150 00:08:52.080 --> 00:08:54.519 they frequently get some of the top people in my 151 00:08:54.600 --> 00:08:59.000 specialty are on those panels. And number two, they get 152 00:08:59.080 --> 00:09:03.879 access to data that you will never see. They're reviewing 153 00:09:05.000 --> 00:09:08.039 protocols and drugs that you're not going to know about. 154 00:09:08.360 --> 00:09:11.879 And so when they say something, don't get upset about it. 155 00:09:12.200 --> 00:09:15.799 Think what did they say and how does this apply 156 00:09:15.919 --> 00:09:19.879 to us, and try to be try to be responsive 157 00:09:19.919 --> 00:09:22.200 to that. The other thing I would say that I 158 00:09:22.279 --> 00:09:26.960 see sort of peripherally is people are always trying to 159 00:09:28.039 --> 00:09:30.480 skirt the rules, pull the wool over their eyes, try 160 00:09:30.519 --> 00:09:34.039 to get away with something. And I think being honest 161 00:09:34.120 --> 00:09:36.279 and saying here's what I know, here's what I don't know, 162 00:09:36.639 --> 00:09:39.200 will really pay dividends. And that's what I would encourage 163 00:09:39.200 --> 00:09:40.200 any CMO to do. 164 00:09:41.799 --> 00:09:43.519 I think there's a wise words. 165 00:09:43.840 --> 00:09:48.519 My interactions have largely been at with siber and I 166 00:09:48.679 --> 00:09:53.840 entirely concur that there may be a tendency to think 167 00:09:53.879 --> 00:09:57.159 of the as an adversarial relationship like you've got to 168 00:09:57.200 --> 00:10:00.360 get this through. Come and get this through the best 169 00:10:00.360 --> 00:10:05.559 ways to engage positively and very much to read very 170 00:10:05.759 --> 00:10:08.879 very carefully what the agency is telling you in that feedback, 171 00:10:09.600 --> 00:10:11.840 and for that reason you need to be transparent too, 172 00:10:12.000 --> 00:10:15.200 because they will tell you the answer. They want to 173 00:10:15.240 --> 00:10:17.799 see the drug approved, they want to see the drug progress. 174 00:10:17.879 --> 00:10:21.120 They're not trying to kill it. But they also have 175 00:10:21.159 --> 00:10:25.960 all that information, and so engaging as positively as you 176 00:10:26.120 --> 00:10:28.320 can and working with them. I've got to say that 177 00:10:28.919 --> 00:10:32.440 in recent past, by experience with siber is that they've 178 00:10:32.480 --> 00:10:35.639 been very much more interactive than I remember them being 179 00:10:36.159 --> 00:10:40.559 several years ago. So bear in mind that, particularly at 180 00:10:40.559 --> 00:10:42.519 the earlier stage, even if you don't have like an 181 00:10:42.600 --> 00:10:46.159 RMAT or something else, the agency seems very willing at 182 00:10:46.159 --> 00:10:51.080 the moment to engage semi informally if you have some questions. 183 00:10:51.120 --> 00:10:53.879 The responses seem to come back. No longer have I 184 00:10:54.320 --> 00:10:56.919 been experiencing responses which like we'll get to this in 185 00:10:56.960 --> 00:10:58.960 the I and D process, It's usually you get a 186 00:10:58.960 --> 00:11:00.879 lot of insight at an early stage. 187 00:11:00.879 --> 00:11:02.519 I don't know whether others can add to. 188 00:11:02.480 --> 00:11:05.600 That that approach to navigating the agency. 189 00:11:07.720 --> 00:11:11.360 So I thought when they were not having live meetings. 190 00:11:11.360 --> 00:11:15.840 That was a major major step back for us because 191 00:11:16.159 --> 00:11:19.080 we got a series of letters. I think what Peter 192 00:11:19.159 --> 00:11:21.480 said is very important. Have other people read the letter 193 00:11:21.519 --> 00:11:25.519 to you. Don't just take your interpretation. Have an expert, 194 00:11:25.679 --> 00:11:30.919 have your colleagues, some other people. But the letter we 195 00:11:31.000 --> 00:11:36.000 got was so concerning, and I knew who the people were, 196 00:11:36.320 --> 00:11:38.919 and I thought, how did they come with this? You know, 197 00:11:39.120 --> 00:11:41.720 this was such a such a departure from standard of 198 00:11:41.919 --> 00:11:44.720 standard of care. But when we had a live meeting, 199 00:11:45.440 --> 00:11:49.600 literally in five minutes, the whole thing was resolved. And 200 00:11:49.679 --> 00:11:53.039 so if you have the if you're able to have 201 00:11:53.080 --> 00:11:55.799 a live meeting, it is so much better. It just 202 00:11:56.000 --> 00:12:00.200 really smooth everything out and everyone left saying I know exactly. 203 00:11:59.840 --> 00:12:03.120 What after and FDA is very open for business. 204 00:12:03.200 --> 00:12:08.799 I mean, part of what will has substantially changed for these, 205 00:12:10.320 --> 00:12:12.879 you know, for the physicians, for the FDA staff, is 206 00:12:12.919 --> 00:12:15.279 that they are now required to go in Monday through 207 00:12:15.279 --> 00:12:18.960 Friday to the campus in Silver Spring, Maryland, and that 208 00:12:19.000 --> 00:12:22.159 will cause some attrition. At the same time, it will 209 00:12:22.240 --> 00:12:24.559 open up the door for more in person meetings, and 210 00:12:24.600 --> 00:12:26.399 I highly recommend going in person. 211 00:12:26.480 --> 00:12:27.519 There's way more. 212 00:12:27.559 --> 00:12:30.759 That you can pick up where people are sitting who's 213 00:12:30.799 --> 00:12:34.440 doing the talking, and you can get way more out 214 00:12:34.480 --> 00:12:38.279 of those interactions, particularly if you're taking a subject matter 215 00:12:38.320 --> 00:12:41.960 expert with you. For example, if you're CMO, perhaps you 216 00:12:41.960 --> 00:12:44.360 know you just need that bolstering of how does this 217 00:12:44.360 --> 00:12:47.879 struggle look in the clinic, what are investigators saying about it? 218 00:12:48.279 --> 00:12:51.679 Having that peer to peer interaction in person is substantially 219 00:12:51.720 --> 00:12:52.960 more valuable than online. 220 00:12:53.240 --> 00:12:54.240 Yeah, I agree. 221 00:12:54.360 --> 00:12:58.799 I mean one of the key meetings I remember asking 222 00:12:58.840 --> 00:13:02.600 for a in person meeting was critical for reading the room, 223 00:13:02.679 --> 00:13:05.639 understanding what they're nodding, what they're agreeing to. But the 224 00:13:05.679 --> 00:13:08.200 other interesting part was, are you know you have to 225 00:13:08.279 --> 00:13:11.279 do your briefing document way in advance? And things evolved 226 00:13:11.360 --> 00:13:13.440 between that time and between the meeting, and there was 227 00:13:13.600 --> 00:13:15.440 a feeling in my company is, well, you can't share 228 00:13:15.440 --> 00:13:17.679 any information that wasn't in your briefing document. And I 229 00:13:17.679 --> 00:13:19.960 was going to, like, of course i will in the 230 00:13:20.120 --> 00:13:22.399 in the in the discussion, if they ask for it, 231 00:13:22.480 --> 00:13:24.080 I'm going to have the piece of paper with me 232 00:13:24.120 --> 00:13:26.759 with the additional data, because again in that case, it's 233 00:13:26.759 --> 00:13:29.759 more of a collaboration. It's going to help them understand more. Sure, 234 00:13:29.759 --> 00:13:30.919 I'm not going to come to the meeting and say 235 00:13:31.000 --> 00:13:32.399 I blind signed to them, but we're going to have 236 00:13:32.399 --> 00:13:34.919 a discussion. And as soon as they asked for it, 237 00:13:34.960 --> 00:13:37.120 I was able to give an additional data that just changed. 238 00:13:37.159 --> 00:13:37.320 You know. 239 00:13:37.480 --> 00:13:40.120 Again, alaid some of their concerns which we didn't have 240 00:13:40.159 --> 00:13:41.799 the time of the briefing book. So again my point 241 00:13:41.840 --> 00:13:45.559 is not going off script, but being prepared, anticipating where 242 00:13:45.600 --> 00:13:48.039 your gaps are and trying to fill those. And then 243 00:13:48.279 --> 00:13:50.399 also I think is really important, particularly if you bring 244 00:13:50.440 --> 00:13:52.360 in I made this one mistake. I brought an academic 245 00:13:52.360 --> 00:13:55.320 from Cleveland Clinic and that person kind of went rogue 246 00:13:55.320 --> 00:13:58.799 on me with and arguing. So that's that's a be 247 00:13:58.879 --> 00:13:59.639 careful with that. 248 00:13:59.559 --> 00:14:03.320 Sometimes cavet who you two take it. 249 00:14:02.600 --> 00:14:05.000 And we all know each other, right, So like the 250 00:14:05.039 --> 00:14:07.799 division director of the lung cancer division, which was me, 251 00:14:08.840 --> 00:14:11.200 I know all the lung kol, so I may have 252 00:14:11.279 --> 00:14:14.840 certain relationships and the division may. So it helps to 253 00:14:14.879 --> 00:14:17.759 have an insider that you can actually vet which kol 254 00:14:18.080 --> 00:14:21.440 you know may be better received. I wanted to ask 255 00:14:21.480 --> 00:14:24.000 you about and so Peter, you talked about c Burr. 256 00:14:25.000 --> 00:14:27.039 Have you a lot of That's the influence of Peter 257 00:14:27.200 --> 00:14:31.519 Marx taking a playbook from Rick Pasitor with the Oncology group. 258 00:14:31.840 --> 00:14:34.759 Have you guys done the interact meetings and are okay? 259 00:14:34.799 --> 00:14:35.679 Can you talk about that. 260 00:14:35.639 --> 00:14:36.159 A little bit? 261 00:14:36.320 --> 00:14:37.320 I can? I can. 262 00:14:38.240 --> 00:14:41.000 I'll just follow up just with just what you were 263 00:14:41.000 --> 00:14:43.039 talked about before, which I think is very very important. 264 00:14:43.120 --> 00:14:45.399 And I've kind of moved to this in my own practice, 265 00:14:45.399 --> 00:14:48.279 as it were, which is never turned down a face 266 00:14:48.320 --> 00:14:50.080 to face interaction with the FDA. This is sort of 267 00:14:50.120 --> 00:14:52.600 a tendency or will go for written responses only and 268 00:14:52.639 --> 00:14:55.279 it'll it'll be easier, but there's nothing like seeing the 269 00:14:55.279 --> 00:14:57.480 whites of the eyes. There really isn't. And you actually 270 00:14:57.480 --> 00:15:00.159 build a bit of rapport and that can go a 271 00:15:00.240 --> 00:15:03.679 huge way, because you never know when you'll need to 272 00:15:03.679 --> 00:15:07.879 be interacting again. And if you had a positive you've 273 00:15:07.879 --> 00:15:09.559 built a bit of a relationship, then you can have 274 00:15:09.600 --> 00:15:13.799 perhaps more of a difficult yet constructive conversation across the table. 275 00:15:13.840 --> 00:15:14.679 And so I'm. 276 00:15:14.519 --> 00:15:16.639 Really glad we all I guess we all lived through 277 00:15:16.639 --> 00:15:20.799 the COVID era where it was all not but but 278 00:15:20.919 --> 00:15:22.519 now now we're we're all back. 279 00:15:22.799 --> 00:15:25.039 I would thoroughly recommend recommend that. 280 00:15:26.639 --> 00:15:31.320 In terms of the the the interact, which in my 281 00:15:31.399 --> 00:15:32.600 mind largely. 282 00:15:32.240 --> 00:15:35.519 Replaced the so called pre pre I n D meeting. 283 00:15:37.320 --> 00:15:39.639 I think it's a I've actually found I've any I've 284 00:15:39.679 --> 00:15:44.159 only done one directly. I have done a three Type 285 00:15:44.240 --> 00:15:48.679 D meetings which are similar sort of set up. I 286 00:15:48.720 --> 00:15:54.399 think the interact my works pretty well as as a 287 00:15:54.559 --> 00:15:58.480 as a way to move move your program forward. You 288 00:15:58.679 --> 00:16:02.679 the pre pre I n D was never minuted formal responses, 289 00:16:02.960 --> 00:16:03.240 and so. 290 00:16:03.240 --> 00:16:04.799 You never quite knew what you were taking away. 291 00:16:04.840 --> 00:16:08.840 Whereas I think the interact adds that level of minuted responses, 292 00:16:08.840 --> 00:16:10.759 you have a much clearer idea of what's going to 293 00:16:10.759 --> 00:16:15.039 be going forwards. I would add that the Type D mechanism, 294 00:16:15.120 --> 00:16:16.559 I know that's been around for a short period. I 295 00:16:16.600 --> 00:16:18.519 don't know how many people in this room have availed 296 00:16:18.519 --> 00:16:21.080 themselves of it, but I think it's a really, really 297 00:16:21.919 --> 00:16:27.039 excellent idea. It's essentially a single topic, but that means 298 00:16:27.039 --> 00:16:30.240 that you get in the room not just a general cast, 299 00:16:30.399 --> 00:16:33.279 but you get all of the key people who are reviewing, 300 00:16:33.279 --> 00:16:36.159 say the clinical section in the case of this particular conference, 301 00:16:36.720 --> 00:16:39.080 and you can really get some excellent feedback. There's a 302 00:16:39.159 --> 00:16:42.480 little bit more of an onus on the preparing company 303 00:16:42.519 --> 00:16:44.840 because you have to submit the questions with the full 304 00:16:44.879 --> 00:16:46.759 package ahead of time. You don't get to send the 305 00:16:47.320 --> 00:16:49.080 pre i D. You get to send it in early 306 00:16:49.159 --> 00:16:52.480 and then the package later. But I've found that the 307 00:16:52.519 --> 00:16:55.759 interactions have been extremely good and very welcome. 308 00:16:55.360 --> 00:16:57.519 From the agency. They'd rather have that kind of an 309 00:16:57.559 --> 00:17:00.720 interaction with you, at least at the SEBA. Does it 310 00:17:00.960 --> 00:17:02.320 address your question a little bit? 311 00:17:02.759 --> 00:17:05.400 Yes, I mean I think that we're talking about how 312 00:17:05.440 --> 00:17:08.480 to how to interact. I think the interact meetings I've 313 00:17:08.519 --> 00:17:13.759 heard have been successful in that kind of we're going 314 00:17:13.759 --> 00:17:16.119 to file an ID, but we're trying to figure out 315 00:17:16.160 --> 00:17:19.839 what may be gating how the FDA may react to 316 00:17:19.839 --> 00:17:23.519 this somewhat novel trial design or endpoint. And I the 317 00:17:24.000 --> 00:17:27.680 most commonly used topics for Type D in my experience 318 00:17:27.680 --> 00:17:31.119 have been around optimus and dose selection. You want that 319 00:17:31.759 --> 00:17:34.559 dose selection, you want that you want that in writing 320 00:17:34.680 --> 00:17:37.519 that FDA agrees with your dose is somewhat of a risk, 321 00:17:37.559 --> 00:17:41.119 in fact, if you're taking somewhat premature data. But and 322 00:17:41.200 --> 00:17:45.279 on the briefing documents, I think some advice that I 323 00:17:45.319 --> 00:17:48.480 would give is that you especially now right with a 324 00:17:48.519 --> 00:17:53.680 constrained volume of staff, these one hundred plus page briefing 325 00:17:53.720 --> 00:17:57.160 documents are just such a nightmare, and you know it's 326 00:17:57.200 --> 00:18:00.640 the job of the individual contributor. So I'm telling you, 327 00:18:00.680 --> 00:18:04.799 as cmos that the division directors your lateral at the FDA, 328 00:18:04.960 --> 00:18:08.000 but there's two lines of reporting up to them. So 329 00:18:08.039 --> 00:18:12.119 there's the individual contributor who's as we call medical officers, 330 00:18:12.359 --> 00:18:16.559 who's getting this briefing document and consolidating it into basically 331 00:18:16.559 --> 00:18:19.640 an executive summary, which you see in the form of 332 00:18:19.680 --> 00:18:23.319 the FDA meeting background. They write that, and they have 333 00:18:23.359 --> 00:18:26.359 to condense those hundred plus pages of this briefing document 334 00:18:26.480 --> 00:18:30.559 and put the salient parts, and then cascade that up 335 00:18:30.559 --> 00:18:33.720 to their middle leader, which we call the cross disciplinary 336 00:18:34.039 --> 00:18:37.599 team leader, who then vets this document and then it 337 00:18:37.599 --> 00:18:39.799 gets pushed up to the division director. So the division 338 00:18:39.839 --> 00:18:43.680 director is not seeing your one hundred page plus briefing document. 339 00:18:43.759 --> 00:18:46.680 So what I think would be wise, especially at this 340 00:18:46.799 --> 00:18:51.400 critical time, is to basically build that executive. 341 00:18:50.880 --> 00:18:53.079 Summary at the top of. 342 00:18:52.759 --> 00:18:56.000 The briefing document so that if it is going to 343 00:18:56.000 --> 00:19:01.200 be essentially lifted, you've created the salient points, You've put 344 00:19:01.240 --> 00:19:04.799 it in nice bullet point formats, You've delineated out your 345 00:19:04.880 --> 00:19:08.240 key topics, you've backed up each of your questions with 346 00:19:08.359 --> 00:19:11.599 the rationale for what the response you think should be 347 00:19:11.680 --> 00:19:13.880 is you're basically framing it up because it's going. 348 00:19:13.839 --> 00:19:15.519 To have to go up two levels to get to 349 00:19:15.559 --> 00:19:16.640 your lateral. 350 00:19:17.839 --> 00:19:21.559 Rich Now, well, I think it gets back to trying 351 00:19:21.599 --> 00:19:23.680 to sit in their seats from where they are and 352 00:19:23.680 --> 00:19:26.039 they're trying to do their job. And I believe always 353 00:19:26.039 --> 00:19:27.720 I need to make their job as easy as possible 354 00:19:27.759 --> 00:19:29.680 so they can go home at night and sleep well 355 00:19:29.680 --> 00:19:32.079 and not worry about is this somehow two years down 356 00:19:32.160 --> 00:19:34.400 they missed something. It's my job to make certain that 357 00:19:34.480 --> 00:19:36.759 all that's in there. And I can give an example 358 00:19:36.759 --> 00:19:40.079 where sometimes you don't also push the envelope because we're 359 00:19:40.079 --> 00:19:41.799 all trying to achieve the same goal. We were trying 360 00:19:41.839 --> 00:19:46.000 to do get a pediatric indication for a pain injection drug, 361 00:19:46.480 --> 00:19:48.640 and you know, the complicated way to do it was 362 00:19:48.720 --> 00:19:50.880 do your dose. You know, we didn't know where to 363 00:19:50.880 --> 00:19:54.039 start with a dose, and we couldn't really do it 364 00:19:54.079 --> 00:19:56.920 with kids going in the surgery because be on ethical 365 00:19:57.039 --> 00:19:59.559 not to treat pain. How we're going to find this out, Well, 366 00:19:59.559 --> 00:20:01.839 what we propose was let's look at real world data 367 00:20:01.880 --> 00:20:04.880 is being used off label. Let's go to a leading 368 00:20:04.920 --> 00:20:07.200 institution where they're using it there and mind their data 369 00:20:07.200 --> 00:20:10.279 and provide all this information to the FDA use claims 370 00:20:10.359 --> 00:20:12.680 database TOS, saying hey, we're not seeing any toxicity at 371 00:20:12.680 --> 00:20:15.359 this dose. Let's model that exposure in humans and what 372 00:20:15.400 --> 00:20:17.680 we think it would be and that's our starting dose. 373 00:20:18.599 --> 00:20:22.279 And the FDA said, okay, that's reasonable. Second thing, we said, look, 374 00:20:22.279 --> 00:20:24.839 we can't do it in a setting. We're going to 375 00:20:24.920 --> 00:20:27.039 have to make certainly these kids are safe. We're going 376 00:20:27.119 --> 00:20:28.799 to do it in kids that are going to be 377 00:20:28.960 --> 00:20:31.319 in the ICU for three days because I can't do 378 00:20:31.319 --> 00:20:33.319 blood draws on these kids all the time. But they're 379 00:20:33.319 --> 00:20:35.960 already got pickline. I can do this very easily, and 380 00:20:36.039 --> 00:20:38.119 this is the highest first patient population, so I will 381 00:20:38.160 --> 00:20:40.440 know if they're in trouble. And I said, that's not 382 00:20:40.559 --> 00:20:42.880 a good idea. That led to a study that was 383 00:20:42.920 --> 00:20:45.960 doable in a year's time, led to approval for kids 384 00:20:46.039 --> 00:20:47.839 down to the age of six years of age, and 385 00:20:47.880 --> 00:20:50.640 then led to a European acceptance as well. Just because 386 00:20:50.640 --> 00:20:52.359 we dared to say, what is the best thing to 387 00:20:52.440 --> 00:20:55.279 do to solve this problem? And the FDA said, let's 388 00:20:55.319 --> 00:20:55.720 go with that. 389 00:20:57.720 --> 00:21:01.200 No, I'm going to change the subject. I have nothing 390 00:21:01.240 --> 00:21:05.000 to add. The one thing I wanted to be aware 391 00:21:05.000 --> 00:21:08.799 of is that people on the panel read everything. They 392 00:21:08.839 --> 00:21:14.359 are very familiar with the literature. And we were turned 393 00:21:14.359 --> 00:21:17.599 down once by a paper that I happened to know 394 00:21:17.720 --> 00:21:21.920 the first author, and it was just bogus, but it 395 00:21:21.960 --> 00:21:24.680 was very hard to argue because it was the opposite viewpoint. 396 00:21:24.759 --> 00:21:28.240 So where you can so we recently had a situation 397 00:21:28.319 --> 00:21:31.720 where we had a difference on what an end point was. 398 00:21:32.079 --> 00:21:34.400 So I got some people together and we wrote a 399 00:21:34.440 --> 00:21:38.720 paper that's accepted because that says it's peer reviewed, and 400 00:21:38.759 --> 00:21:41.759 this is accepted by a high quality journal, So I 401 00:21:41.799 --> 00:21:45.000