WEBVTT 1 00:00:00.320 --> 00:00:03.359 Welcome to Pharma Talk Radio. This podcast is focused on 2 00:00:03.399 --> 00:00:07.080 designing clinical trials balancing simplicity and complexity from the twenty 3 00:00:07.120 --> 00:00:10.240 twenty five Chief Medical Officer Summer three sixty. For more 4 00:00:10.240 --> 00:00:14.720 information on the CMO Summit, editorials, podcasts, or webcasts, please 5 00:00:14.800 --> 00:00:17.519 visit CMO three sixty dot org. Thank you and enjoy 6 00:00:17.559 --> 00:00:18.239 the podcast. 7 00:00:18.480 --> 00:00:22.760 We thought it would be really helpful to get the 8 00:00:23.000 --> 00:00:29.719 cmos and data input onto how do we actually physically 9 00:00:29.960 --> 00:00:33.159 do this and what the challenges are to being able 10 00:00:33.200 --> 00:00:35.759 to do that. And part of it is that we 11 00:00:35.799 --> 00:00:39.600 live in a complex world, so it's quite challenging. So 12 00:00:39.799 --> 00:00:43.640 let's start out by doing introductions. Chris, why don't we 13 00:00:43.679 --> 00:00:45.399 started that and we'll work this way. 14 00:00:45.719 --> 00:00:47.600 Yeah. Thanks. I'm Chris Morribido. 15 00:00:47.719 --> 00:00:50.960 I'm the Chief Medical officer at a company called Astrio Therapeutics. 16 00:00:51.280 --> 00:00:52.600 It's allergy and immunology. 17 00:00:53.000 --> 00:00:56.200 We have one phase three asset, one phase one asset, 18 00:00:56.679 --> 00:01:00.320 and I'm incredibly sobered up by the conversation since that 19 00:01:00.359 --> 00:01:01.119 we heard this morning. 20 00:01:02.479 --> 00:01:07.040 Hello everyone, I'm Eric Scalfrow, CEO and founder Rivia. I 21 00:01:07.079 --> 00:01:10.719 found a Rivia to help sponsors stay in control when 22 00:01:10.920 --> 00:01:15.000 trials get complicated by helping them bring all their data 23 00:01:15.200 --> 00:01:20.799 together to bring clarity and momentum. I'm really excited for 24 00:01:20.840 --> 00:01:25.640 the conversation today, in particular to understand how we can 25 00:01:25.680 --> 00:01:31.359 improve outcomes with smarter oversights, and that smarter oversight starts 26 00:01:31.400 --> 00:01:37.359 at the design stage. We're seeing over twenty active trials 27 00:01:37.359 --> 00:01:39.719 at RIVIA right now, and I'm excited to share some 28 00:01:39.719 --> 00:01:42.159 of these observations I've had over the last couple of years. 29 00:01:42.719 --> 00:01:44.680 Wonderful. Hi. 30 00:01:44.799 --> 00:01:49.319 I'm Judy Nung Cash and I'm the chief medical officer 31 00:01:49.640 --> 00:01:57.760 of Novotech, where CRO really focused on serving the biotech community. 32 00:01:58.920 --> 00:02:02.840 While I'm at nov Tech now I can say I've 33 00:02:02.879 --> 00:02:07.120 had twenty years in the industry across large sponsors, small 34 00:02:07.159 --> 00:02:11.039 biotech and larger CRO. So I hope to bring kind 35 00:02:11.080 --> 00:02:14.319 of a balanced perspective to our topic today. 36 00:02:15.159 --> 00:02:15.800 Great, Thank you. 37 00:02:16.719 --> 00:02:22.000 Hi everyone. I'm Bertillion Markham, the chief medical officer of Bicopharma. 38 00:02:22.199 --> 00:02:29.560 We're a Scandinavian biofarma focusing on IPF and angiotens into 39 00:02:30.479 --> 00:02:33.879 type two receptor agonists, which is quite unique. I think 40 00:02:34.039 --> 00:02:39.000 everyone can do anything complex, but doing it simple, simply 41 00:02:39.120 --> 00:02:40.439 and simple, that's the trick. 42 00:02:41.280 --> 00:02:43.280 And Buru, what phase are you in? 43 00:02:44.000 --> 00:02:46.680 We're in phase two with the compound. So we're starting 44 00:02:46.719 --> 00:02:50.599 a big two hundred and seventy patient study in IPF, 45 00:02:51.000 --> 00:02:54.159 so lots of things to coordinate and ninety seven sites. 46 00:02:55.080 --> 00:02:55.319 Great. 47 00:02:55.520 --> 00:02:58.879 So, you know, Ken talked a lot about pivotal and 48 00:02:59.000 --> 00:03:02.879 phase three trials and we're gonna I'm going to kind 49 00:03:02.879 --> 00:03:06.280 of break this down into the challenges we see with 50 00:03:06.639 --> 00:03:09.520 earlier phase trials and what we need to do with 51 00:03:09.840 --> 00:03:15.560 biotechs and with vendors, answer key questions we need to 52 00:03:16.560 --> 00:03:21.400 get for how do we risk manage our programs, make 53 00:03:21.479 --> 00:03:24.400 investors happy and be able to fund our company and 54 00:03:25.840 --> 00:03:28.879 also move things forward, and then we'll switch over to 55 00:03:29.000 --> 00:03:33.439 the pivotal at the end. Although with development right now 56 00:03:33.719 --> 00:03:36.360 in particular in a lot of these phases are kind 57 00:03:36.400 --> 00:03:39.719 of blurring in the biotech world, so a lot of the. 58 00:03:39.759 --> 00:03:40.719 Questions are the same. 59 00:03:40.879 --> 00:03:47.439 So let's talk a little bit about what the challenges 60 00:03:47.560 --> 00:03:52.360 are in early phase trials of what you're trying to 61 00:03:52.639 --> 00:03:56.599 solve for first and how that makes your trials complex 62 00:03:57.520 --> 00:04:01.000 and how you deal with that to be able to. 63 00:04:02.479 --> 00:04:07.120 Make them more doable. So what you know, do we 64 00:04:07.240 --> 00:04:10.360 want to start with the Let's start with the christ. 65 00:04:10.120 --> 00:04:11.120 And will work away across. 66 00:04:11.159 --> 00:04:14.599 It's I mean that's a key question. We have so 67 00:04:14.719 --> 00:04:19.399 many stakeholders, and I mean all of us are incredibly 68 00:04:19.920 --> 00:04:23.240 curious people, and we're scientists by heart, and we want 69 00:04:23.279 --> 00:04:25.360 to do the right thing for patients by heart, and 70 00:04:25.480 --> 00:04:27.199 we want to do the right thing for our company 71 00:04:27.319 --> 00:04:29.879 and for investors, and for the FDA and for the EMA. 72 00:04:30.800 --> 00:04:34.759 So many stakeholders, and there are only so many questions 73 00:04:34.839 --> 00:04:38.040 one can ask or one should ask in early phase trial. 74 00:04:38.279 --> 00:04:40.040 So you know, one thing that we've started doing is 75 00:04:40.839 --> 00:04:44.279 asking the hard questions, what are these data for? 76 00:04:45.040 --> 00:04:48.240 Who are these data going to be shown to, what 77 00:04:48.439 --> 00:04:55.319 is an expected expectation of these data? And what kinds specifically, 78 00:04:55.600 --> 00:04:59.160 what kinds of questions must we answer versus what kinds 79 00:04:59.199 --> 00:05:01.560 of questions would be to answer? And for a lot 80 00:05:01.600 --> 00:05:04.680 of us in biotechnology, we live and breathe by our data. 81 00:05:04.800 --> 00:05:08.079 That's what funds us. And uh, you know, it's it's 82 00:05:08.160 --> 00:05:11.720 often difficult to have to ask the question, how do 83 00:05:11.839 --> 00:05:14.759 I get the right data for an investor versus the 84 00:05:14.879 --> 00:05:17.600 right data to get this in front of an end 85 00:05:17.600 --> 00:05:19.839 of phase two meeting. So the FD is going to 86 00:05:19.879 --> 00:05:22.399 be happy with our selection of our clinical trial designer 87 00:05:22.399 --> 00:05:22.959 for phase three. 88 00:05:23.079 --> 00:05:28.279 It's a tough. It's a tough intellectual balance. So you know, it's. 89 00:05:29.759 --> 00:05:32.439 What we've what we've opted to do is work through 90 00:05:32.519 --> 00:05:36.600 this step by step in in fact, in fact hierarchy, hierarchical, 91 00:05:37.000 --> 00:05:40.519 hierarchically rank who we're trying to please and who we're 92 00:05:40.519 --> 00:05:42.439 trying to address with our data, such that we could 93 00:05:42.480 --> 00:05:45.920 design the most simple trials. Almost always has been said, 94 00:05:45.959 --> 00:05:48.399 and as we learn from Ken this morning, simple is better, 95 00:05:49.000 --> 00:05:50.319 but simple isn't always best. 96 00:05:51.160 --> 00:05:52.399 So it's it's uh. 97 00:05:54.240 --> 00:05:57.439 Limiting to the most precise questions that we can ask 98 00:05:58.319 --> 00:05:59.920 in order to please the right stakeholders. 99 00:06:01.959 --> 00:06:04.800 Maybe if I could just react to that, you know, 100 00:06:05.199 --> 00:06:09.600 I think you can't simplify what you can't see, right, 101 00:06:11.079 --> 00:06:15.439 I think there's a gap between the designs and the 102 00:06:16.439 --> 00:06:21.600 reality operationally that they bring. Bettiel had some eloquent way 103 00:06:21.680 --> 00:06:25.360 to put it before that they're very theoretical. 104 00:06:25.720 --> 00:06:27.199 And I just had one anecdote. 105 00:06:27.240 --> 00:06:29.560 I was speaking to a CMO on Friday who has 106 00:06:29.639 --> 00:06:33.439 an open label phase two in a variant of IBD, 107 00:06:34.759 --> 00:06:38.199 and in this dose escalation, he first needs to review 108 00:06:38.319 --> 00:06:41.480 every patient before they're escalated and then discuss that with 109 00:06:41.600 --> 00:06:44.399 the PIS and make a joint decision if that makes 110 00:06:44.839 --> 00:06:47.800 sense right now, that actually brings quite a lot of 111 00:06:48.240 --> 00:06:52.720 operational burden, right, fifty patients, each patient takes a couple 112 00:06:52.759 --> 00:06:55.759 of hours to do that. That's already several hundred hours 113 00:06:56.680 --> 00:07:02.319 to do that review on paper, pretty simple, and so 114 00:07:02.519 --> 00:07:06.959 bridging that gap of considering the operational reality with the designs, 115 00:07:07.000 --> 00:07:09.199 I think is a is an important step. 116 00:07:09.680 --> 00:07:09.879 Yeah. 117 00:07:09.920 --> 00:07:10.720 Well, you know, it's funny. 118 00:07:10.759 --> 00:07:13.600 I'm from Philly and uh you know we have a 119 00:07:13.680 --> 00:07:18.240 famous basketball uh thing where Alan Everson said practice, I 120 00:07:18.279 --> 00:07:21.639 don't need practice, right, And what we find is that 121 00:07:23.279 --> 00:07:26.800 sometimes you win these before you start. And Judith, you know, 122 00:07:26.920 --> 00:07:31.360 as somebody that's a cro how much up front work 123 00:07:31.839 --> 00:07:34.879 does it take to get your trials to be simplistic 124 00:07:35.839 --> 00:07:37.120 even in a complex world. 125 00:07:38.040 --> 00:07:40.720 I think that's a great question. And I think, you know, 126 00:07:41.120 --> 00:07:44.639 Chris got to the heart of it. I think, you know, 127 00:07:44.800 --> 00:07:48.959 coming from a big pharma background where you know you're 128 00:07:49.000 --> 00:07:54.000 really designing for the health authorities right for approval, you're 129 00:07:54.040 --> 00:07:58.319 looking at this long long development program and trying to 130 00:07:58.399 --> 00:08:02.240 do things in a stepwise fashion. And what's very different 131 00:08:02.560 --> 00:08:07.839 working with biotech is all the stakeholders, right, and I 132 00:08:08.000 --> 00:08:13.040 think what we observe with our early phase biotech. 133 00:08:13.399 --> 00:08:14.759 Sponsors, is it. 134 00:08:16.279 --> 00:08:21.680 That prioritization is rarely done right, and so you're trying 135 00:08:21.720 --> 00:08:27.240 to please everyone, which just adds more endpoints, because what's 136 00:08:27.519 --> 00:08:32.200 meaningful to the regulators might be different than what is 137 00:08:32.399 --> 00:08:36.440 going to be a value inflection point for you with investors. 138 00:08:36.639 --> 00:08:40.799 And so I see, I do observe sponsors trying to 139 00:08:40.879 --> 00:08:47.240 add everything in but not appreciating the potential operational risk 140 00:08:47.799 --> 00:08:52.399 that they incur and that that ultimately might result in 141 00:08:52.480 --> 00:08:56.600 a problem with your data integrity. So it is a 142 00:08:56.759 --> 00:09:02.039 conversation when you have a biotech who doesn't have operational 143 00:09:02.159 --> 00:09:05.720 experience in it to really say can we can we 144 00:09:05.840 --> 00:09:09.639 trade off? And it's a lot of work, and depending 145 00:09:09.720 --> 00:09:14.039 on the background of who you're interacting with, that sort 146 00:09:14.080 --> 00:09:19.080 of conversation may or may not hit well yeah. 147 00:09:19.600 --> 00:09:23.639 Yeah, no, I think there is kind of many many 148 00:09:23.720 --> 00:09:28.639 flavors of complexity, avoidable and unavoidable because you start with 149 00:09:28.759 --> 00:09:31.159 the drug and you start in therapeutic area, so you 150 00:09:31.279 --> 00:09:34.279 have some kind of complexity to begin with, but then 151 00:09:34.600 --> 00:09:37.120 you add on and I remember many years back in 152 00:09:37.240 --> 00:09:41.399 ASTRA people suggested that we have a cutting manager that 153 00:09:41.840 --> 00:09:44.720 actually tried to cut down on the number of things 154 00:09:44.799 --> 00:09:48.360 that people heaped up on studies. So I think that 155 00:09:48.600 --> 00:09:52.279 mindset is extremely important. So you make it as simple 156 00:09:52.399 --> 00:09:56.120 as you possibly can while still answering the key questions. 157 00:09:56.480 --> 00:09:58.080 And then I think there and there's a degree of 158 00:09:58.200 --> 00:10:04.080 blindness because the companies often try something new and already 159 00:10:04.120 --> 00:10:06.960 in the design phase, you are kind of blind to 160 00:10:07.120 --> 00:10:10.679 the problems that you will anticipate. Actually the pis and 161 00:10:11.320 --> 00:10:13.679 the sites might actually help you. And then of course 162 00:10:13.720 --> 00:10:17.799 we spoke about the patients and the sort of simplicity 163 00:10:18.159 --> 00:10:22.679 that understanding the patient bird brings, So I think there 164 00:10:22.720 --> 00:10:24.600 are those things that can help. 165 00:10:24.960 --> 00:10:27.440 Yeah, it's a great point. I think Ken talked about 166 00:10:27.440 --> 00:10:28.519 it a little bit this morning. 167 00:10:28.519 --> 00:10:31.600 I'd be interested to hear how when you start to 168 00:10:31.679 --> 00:10:35.480 think about your programs you start to think about patient burden, 169 00:10:35.919 --> 00:10:42.240 site burden, do ability. Are you designing programs that are 170 00:10:42.279 --> 00:10:45.240 actually people are able to do? And how do you 171 00:10:46.320 --> 00:10:48.559 take that into account and what kind of feedback you 172 00:10:48.679 --> 00:10:49.960 get to be able to achieve that? 173 00:10:50.320 --> 00:10:52.120 So look, you hear left from the group. 174 00:10:53.200 --> 00:10:55.559 So yeah, yes, absolutely. 175 00:10:55.600 --> 00:11:00.679 From the beginning, as a patient orient in company, we 176 00:11:01.200 --> 00:11:03.320 take a lot of time and care to talk with 177 00:11:03.399 --> 00:11:07.960 the patient groups. We've established patient advisory councils working closely 178 00:11:08.000 --> 00:11:12.960 with patient advocacy organizations. And the advocacy organizations have been 179 00:11:13.440 --> 00:11:16.559 incredibly helpful by themselves, but the advisory councils. 180 00:11:16.399 --> 00:11:17.720 Are one step better. 181 00:11:18.240 --> 00:11:22.000 These are people that we can talk about strategy with 182 00:11:22.240 --> 00:11:25.639 but then talk about operations with as well. And you know, 183 00:11:25.720 --> 00:11:29.200 when we propose clinical trial operation elements, these are the 184 00:11:29.279 --> 00:11:30.200 number of site visits. 185 00:11:30.279 --> 00:11:31.080 This is what we want to do. 186 00:11:31.159 --> 00:11:33.879 At each side visit, they come with pencils and pens 187 00:11:33.919 --> 00:11:35.799 and they mark it up and they give us the 188 00:11:35.840 --> 00:11:37.799 feedback and this is not going to happen or you 189 00:11:37.919 --> 00:11:38.399 need to do that. 190 00:11:39.200 --> 00:11:41.720 It's incredibly helpful because if we can. 191 00:11:41.639 --> 00:11:43.840 Then go to our sites and said, we designed this 192 00:11:43.960 --> 00:11:46.399 with input from your patients, and this is what they 193 00:11:46.600 --> 00:11:50.120 feel like they can do in a clinical trial. Operational 194 00:11:50.159 --> 00:11:52.879 burden therefore is therefore is decreased, so please help us 195 00:11:52.919 --> 00:11:53.600 enroll this trial. 196 00:11:53.960 --> 00:11:57.919 So far that seems to work. It's an evolving landscape. 197 00:11:57.519 --> 00:12:03.360 Though, I think there what's important is that you know, 198 00:12:03.720 --> 00:12:10.720 complexity is a choice, not a consequence, in the sense 199 00:12:10.799 --> 00:12:16.000 that right we saw mister Getz's staring numbers on more endpoints, 200 00:12:16.080 --> 00:12:21.879 more procedures, et cetera. Now, what does that really imply operationally? 201 00:12:22.039 --> 00:12:27.600 How does that compound risk and variability? Right? I have 202 00:12:28.360 --> 00:12:33.639 several of our sponsors are now undertaking decentralized trials, and 203 00:12:34.080 --> 00:12:39.000 what I hear is there is a discordant reduction in 204 00:12:39.039 --> 00:12:42.519 burden decentralized trials the premise that it reduces patient burden 205 00:12:43.600 --> 00:12:47.639 for the people running the trial, it actually potentially increases 206 00:12:47.679 --> 00:12:51.799 it because instead of just doing the monitoring at the site, 207 00:12:51.879 --> 00:12:54.039 you now have to do monitoring at the site and 208 00:12:55.039 --> 00:12:57.799 at the patient's home, and you have to make sure 209 00:12:57.840 --> 00:13:02.600 the data is collected in consistent ways, and so there 210 00:13:02.679 --> 00:13:07.720 the complexity is perhaps more of a consequence than a choice, 211 00:13:08.360 --> 00:13:10.159 or maybe not fully thought out. So I think it's 212 00:13:10.200 --> 00:13:15.639 important to reflect on those different compounding elements of complexity. 213 00:13:18.279 --> 00:13:22.679 I think that you know, especially for you know, our 214 00:13:22.799 --> 00:13:28.320 biotech sponsors, the the technologies that are being studied are 215 00:13:28.639 --> 00:13:34.159 by definition super complex. Right, So there is operational complexity 216 00:13:34.879 --> 00:13:37.519 that you can't like what you were saying, virtiularly, that 217 00:13:37.639 --> 00:13:41.200 you can't avoid there maybe there's a cold chain, supply 218 00:13:41.320 --> 00:13:44.440 chain or something like that that is unavoidable. But I 219 00:13:44.559 --> 00:13:50.159 think when you can, I think the complexity from the 220 00:13:50.200 --> 00:13:55.120 sponsors is often driven by a risk aversion, right, that 221 00:13:55.440 --> 00:13:58.480 we're going to not collect the right data, that someone's 222 00:13:58.600 --> 00:14:01.840 gonna one of our many stakeholders is going to ask 223 00:14:02.000 --> 00:14:05.679 for data we didn't collect, and why don't you collect that? 224 00:14:05.840 --> 00:14:07.440 And I'm not going to invest in your company. 225 00:14:07.519 --> 00:14:12.799 And I think taking a risk based approach to what 226 00:14:15.039 --> 00:14:18.399 must we have and can I accept the risk that 227 00:14:18.480 --> 00:14:20.919 maybe someone down the road some day is going to 228 00:14:20.960 --> 00:14:21.960 ask for this other thing? 229 00:14:22.399 --> 00:14:23.399 And let's omit that. 230 00:14:24.240 --> 00:14:28.919 I think it's hard math when you're a physician scientist 231 00:14:29.000 --> 00:14:32.919 and you just want more data because it's convention that 232 00:14:33.000 --> 00:14:33.720 more data. 233 00:14:33.559 --> 00:14:34.279 Is better, right. 234 00:14:35.759 --> 00:14:35.960 Yeah. 235 00:14:36.639 --> 00:14:40.639 I guess if you like a clinical study with going 236 00:14:40.720 --> 00:14:44.720 on an expedition, you kind of you can't pack everything, 237 00:14:45.480 --> 00:14:48.600 so you have to unpack and limit and that's a 238 00:14:48.679 --> 00:14:53.600 hard choice. And I guess the complexity has three time 239 00:14:53.919 --> 00:14:57.679 segments in a way, it's before the study, is during 240 00:14:57.759 --> 00:15:00.919 the study, and it's after the study. One of the 241 00:15:01.000 --> 00:15:05.039 key aspects that I'm quite interested in is the data 242 00:15:05.240 --> 00:15:08.600 and the access to data. At least my experience is 243 00:15:08.679 --> 00:15:10.320 that sort of there is a little bit of a 244 00:15:10.399 --> 00:15:13.679 power game sort of who accesses the data and who 245 00:15:13.759 --> 00:15:18.200 can really understand the data in depth in a clinical trials, 246 00:15:18.960 --> 00:15:23.480 both during the trial blinded data and after the data 247 00:15:23.559 --> 00:15:27.200 when you try to connect this to the next sort 248 00:15:27.240 --> 00:15:31.519 of phase in the program. And I think accessing blinded 249 00:15:31.639 --> 00:15:35.159 data during studies is extremely important. I know that Rivia 250 00:15:35.279 --> 00:15:38.279 is working with that Capacious and other companies that you 251 00:15:38.320 --> 00:15:41.120 will see here where you can have sort of data 252 00:15:41.200 --> 00:15:44.679 dump and actually understanding the data during the trial because 253 00:15:44.720 --> 00:15:48.240 that helps you actually plan for the next segment. And 254 00:15:48.320 --> 00:15:51.519 I think that's super important to reduce complexity. 255 00:15:52.600 --> 00:15:58.080 So, Chris, you talked about site and Bernald you talked 256 00:15:58.080 --> 00:16:01.480 about this to cite and patient input and having you know, 257 00:16:01.799 --> 00:16:07.480 folks review your protocols. Any of you institute actually walking 258 00:16:07.559 --> 00:16:12.279 through your visits and looking at your visits and seeing 259 00:16:12.360 --> 00:16:14.879 what you're asking patients to do with your visits. Have 260 00:16:15.399 --> 00:16:17.600 you done that in your child I'd be curious to 261 00:16:18.200 --> 00:16:20.840 folks in the audience as well of actually having your 262 00:16:20.919 --> 00:16:25.120 folks just pretend they're a patient or a coordinator and 263 00:16:25.240 --> 00:16:28.840 actually make them do a visit, as has anybody on 264 00:16:28.960 --> 00:16:31.360 this panel thought about her? 265 00:16:31.480 --> 00:16:34.519 Have they done that to see what the burden really is. 266 00:16:35.360 --> 00:16:39.480 I've asked my clinop's team to do it, but I 267 00:16:39.519 --> 00:16:40.399 haven't done it myself. 268 00:16:41.000 --> 00:16:45.240 Yeah, yeah, I think I think you see that happening 269 00:16:45.279 --> 00:16:45.919 at sponsors. 270 00:16:46.759 --> 00:16:50.519 Not really, but it's a great idea because I think, 271 00:16:53.039 --> 00:16:57.600 you know, that experience really helps you understand what's necessary, 272 00:16:57.720 --> 00:17:02.000 what's not necessarily, what's a burden. I think asking people 273 00:17:02.679 --> 00:17:07.000 is a good idea. And you know, one thing, you know, 274 00:17:07.119 --> 00:17:09.279 this conversation is making me think. You know, it's so 275 00:17:09.599 --> 00:17:14.799 competitive to enroll the patients, and the sites feel it, 276 00:17:15.720 --> 00:17:19.000 the sponsors feel it, and so anything you can do 277 00:17:19.720 --> 00:17:22.000 to like hit the easy button for both of those 278 00:17:22.119 --> 00:17:26.920 populations might actually give you a competitive advantage in a 279 00:17:27.039 --> 00:17:29.559 crowded you know, indication. 280 00:17:30.240 --> 00:17:32.680 Yeah, I think the idea of walking through a visit 281 00:17:33.039 --> 00:17:35.720 or the visits is really important. The number of visits 282 00:17:35.759 --> 00:17:39.319 and the complexity is extremely important. And I was starting 283 00:17:39.400 --> 00:17:44.039 to think of a clinical study as a board game basically, 284 00:17:44.200 --> 00:17:47.880 because you do you have the the sequence of events, 285 00:17:47.960 --> 00:17:50.920 but you also have the the what if kind of 286 00:17:51.039 --> 00:17:54.519 questions that will that will happen during a trial that 287 00:17:54.720 --> 00:17:57.160 you don't spend enough time to walk through. 288 00:17:57.599 --> 00:18:02.440 And eric you help folks think through their databases but 289 00:18:02.519 --> 00:18:06.640 also their data entries, So do you do that with 290 00:18:06.799 --> 00:18:11.519 sponsors where you actually have them sit through and simulate 291 00:18:11.599 --> 00:18:13.920 a patient and have them entered their data or think 292 00:18:14.000 --> 00:18:14.319 through that. 293 00:18:15.000 --> 00:18:15.559 Sure. 294 00:18:16.119 --> 00:18:18.640 More so, we have two chief medical officers in our 295 00:18:18.680 --> 00:18:22.480 founding team and did pretty much the exercise you're describing 296 00:18:22.559 --> 00:18:28.440 with their teams, more so on a softer side, to 297 00:18:28.599 --> 00:18:32.200 humanize the trial, to really understand because a lot of people, 298 00:18:33.000 --> 00:18:36.279 including myself, are very far moved from the patients and 299 00:18:36.319 --> 00:18:39.240 the reality of the data collection at the site and 300 00:18:39.599 --> 00:18:43.720 you just becomes a lot of emails and data points, 301 00:18:44.960 --> 00:18:47.359 and so they've brought them for a few visits to 302 00:18:47.480 --> 00:18:51.319 really understand the reality of what it takes. More from 303 00:18:51.480 --> 00:18:57.119 really an empathetic, humanizing perspective, I think it softened a 304 00:18:57.160 --> 00:19:00.599 little bit to the frustrations when things are or when 305 00:19:00.680 --> 00:19:03.160 things are maybe not the quality that they desire, because 306 00:19:03.200 --> 00:19:07.039 there's there's a tough reality. 307 00:19:06.759 --> 00:19:07.319 To it as well. 308 00:19:08.559 --> 00:19:11.640 So, Chris, you I'm going to shift this a little 309 00:19:11.680 --> 00:19:14.799 bit because we've been talking about patient burden and site burden, 310 00:19:15.480 --> 00:19:18.279 but you raise another thing at the beginning, and that's 311 00:19:18.920 --> 00:19:22.079 all the stakeholders you have to answer questions for and 312 00:19:22.200 --> 00:19:27.599 be able to produce clinical trial results for. And I'd 313 00:19:27.640 --> 00:19:31.000 love to hear from the four of you. Who where 314 00:19:31.119 --> 00:19:38.160 you think your biggest challenge of complexity comes from. Does 315 00:19:38.240 --> 00:19:42.279 it come from your self, does it come from the 316 00:19:43.119 --> 00:19:46.359 from the board, does it come from your investors, does 317 00:19:46.440 --> 00:19:49.319 it come from the regulators? Where do you think or 318 00:19:49.440 --> 00:19:52.160 does it come from the scientific community. Where do you 319 00:19:52.279 --> 00:19:55.599 each think that the complexity arises from? If you had 320 00:19:55.680 --> 00:19:58.400 to pick a point where it comes from, where would 321 00:19:58.400 --> 00:19:59.359 you think that comes from? 322 00:20:00.519 --> 00:20:03.599 So I think each of those and those stakeholders that 323 00:20:03.640 --> 00:20:07.920 you identified wants a simple trial. The challenge, of course, 324 00:20:08.039 --> 00:20:10.559 is that they want a simple trial asking different questions. 325 00:20:11.799 --> 00:20:15.000 So ultimately the complexity is on us because we're trying 326 00:20:15.000 --> 00:20:18.240 to put all of those questions into one trial. You know, 327 00:20:18.319 --> 00:20:21.200 it's it's no longer sufficient just to say I'm going 328 00:20:21.240 --> 00:20:23.720 to do a safety study in phase one. You know, 329 00:20:23.839 --> 00:20:26.799 you're throwing in biomarkers, You're throwing into all these exploratory 330 00:20:26.880 --> 00:20:29.640 things to look for some efficacy signal that will translate 331 00:20:29.720 --> 00:20:35.519 into potentially a value inflection. And that makes it very 332 00:20:35.559 --> 00:20:37.720 complex even for a phase one study, which are generally 333 00:20:37.799 --> 00:20:42.279 operationally simple. So you know, this is why we do this. 334 00:20:42.359 --> 00:20:44.680 Prioritization is trying to, you know, try to limit the 335 00:20:44.799 --> 00:20:46.720 number of people that are forcing us to ask these 336 00:20:46.759 --> 00:20:47.640 complex questions. 337 00:20:49.759 --> 00:20:55.000 Yeah, and so from my perspective, what becomes challenging is 338 00:20:55.640 --> 00:20:59.839 deciding what's essential and cutting what's not and seeing how 339 00:21:00.559 --> 00:21:04.920 that priorization might change as the trial's unfolding, right, and 340 00:21:05.279 --> 00:21:10.400 responding to various stakeholders. So kind of being like by analogy, 341 00:21:11.079 --> 00:21:13.359 you know, the bird at thirty thousand feet or a 342 00:21:13.440 --> 00:21:16.039 hulk and knowing at the right time to go and 343 00:21:16.720 --> 00:21:19.440 peek down and then come back up and resurface. I 344 00:21:19.480 --> 00:21:22.519 think that's tremendously difficult, but also where there's a lot 345 00:21:22.599 --> 00:21:24.400 of potential and opportunity. 346 00:21:26.440 --> 00:21:29.240 If I had to pick one of the stakeholders that 347 00:21:30.039 --> 00:21:37.319 the one stakeholder that drives complexity, I might say the investors, 348 00:21:37.640 --> 00:21:42.480 only because what they want out of an early phase 349 00:21:42.599 --> 00:21:47.240 trial is so much right. And you know, for what 350 00:21:47.759 --> 00:21:49.720 when we used to do phase one, it was just 351 00:21:50.200 --> 00:21:53.440 healthy volunteer sad mads and simple and let's move on 352 00:21:53.559 --> 00:21:57.920 to the next phase. But the funding pressure and the 353 00:21:58.119 --> 00:22:03.319 time pressure, I think drives adding all this other stuff 354 00:22:03.400 --> 00:22:07.720 in that drives complexity. So even though we'll say this 355 00:22:07.920 --> 00:22:11.640 is not powered, it's exploratory, people want something at the 356 00:22:11.759 --> 00:22:14.519 end of that right because they invested and they want 357 00:22:14.599 --> 00:22:17.279 to turn around and or you know, an increase in 358 00:22:17.400 --> 00:22:21.319 value or whatever it is. So I think that on 359 00:22:21.519 --> 00:22:25.319 the sponsor side, especially for the CMO population, we're just 360 00:22:25.480 --> 00:22:29.160 trying to do a good trial that is safe or 361 00:22:29.359 --> 00:22:31.920 has the appropriate risk benefit for the people who are 362 00:22:32.440 --> 00:22:35.160 you know, volunteering to be in this experiment. 363 00:22:36.279 --> 00:22:38.119 And then you add on from that. 364 00:22:40.400 --> 00:22:44.599 Yeah, I think it's easy to kind of blame everyone else, 365 00:22:44.680 --> 00:22:49.960 but I think the cmos are driving complexity as well. 366 00:22:50.240 --> 00:22:53.720 And obviously you have you have your guiding star with 367 00:22:54.160 --> 00:22:56.920 the regulators and the science and the drug and you 368 00:22:57.000 --> 00:23:00.920 try to get that into package. But actually then there 369 00:23:00.960 --> 00:23:04.519 are kind of some kind of inertia and some kind 370 00:23:04.559 --> 00:23:07.680 of momentum that builds in company where you add stuff, 371 00:23:08.319 --> 00:23:12.559 but you have to restrict and keep yourself a bit calm, 372 00:23:12.680 --> 00:23:13.599 even as a CMO. 373 00:23:13.960 --> 00:23:15.680 I think and do you think that. 374 00:23:17.160 --> 00:23:20.400 It's a good point. Do you think that getting involved 375 00:23:20.599 --> 00:23:26.240 earlier in the program, when the prequinical programs are designed 376 00:23:27.160 --> 00:23:30.799 would help you streamline some of the things that you're 377 00:23:30.880 --> 00:23:33.799 trying to collect or target so that you get that 378 00:23:34.480 --> 00:23:38.480 one answer out of your phase one two that's meaningful 379 00:23:38.759 --> 00:23:41.440 when you've thought about it when they put the drug 380 00:23:41.519 --> 00:23:43.519 into a mouse or or. 381 00:23:43.480 --> 00:23:47.240 A monkey or something like that. Thought about that about. 382 00:23:47.680 --> 00:23:52.000 Our companies bringing cmos in too late to think about 383 00:23:52.039 --> 00:23:53.880 the holistic design their programs. 384 00:23:53.960 --> 00:23:54.759 Is that adding to it? 385 00:23:55.799 --> 00:23:55.960 Yeah? 386 00:23:56.000 --> 00:23:58.839 Maybe, But I think honestly that kind of question that 387 00:23:58.880 --> 00:24:01.960 you're asking goes with every single phase change. I mean, 388 00:24:02.079 --> 00:24:05.079 I think that we should be thinking deeply along the 389 00:24:05.119 --> 00:24:08.359 way of all of the data that informed a high 390 00:24:08.400 --> 00:24:10.880 pos in the clinical trial that you're about to start. 391 00:24:11.000 --> 00:24:13.480 And I think that absolutely does include the pre clinical space. 392 00:24:14.119 --> 00:24:16.079 One of my former mentors that actually is in the 393 00:24:16.160 --> 00:24:19.319 audience today taught me a long time ago that you 394 00:24:19.359 --> 00:24:21.640 should never ask a question you don't really know the 395 00:24:21.720 --> 00:24:24.240 answer to. You should pretty much be sure you're going 396 00:24:24.319 --> 00:24:27.480 to get an answer that you've predicted. And there are 397 00:24:27.599 --> 00:24:32.359 lots of tools like doing more translational research, enabling model 398 00:24:32.359 --> 00:24:36.039 informed drug development and pharmacometrics to give you confidence in 399 00:24:36.160 --> 00:24:38.160 the question that you're about to ask. 400 00:24:38.359 --> 00:24:39.359 So yeah, absolutely. 401 00:24:39.960 --> 00:24:45.279