WEBVTT 1 00:00:00.120 --> 00:00:03.399 Welcome to Farmer Talk Radio. This podcast is focused on 2 00:00:03.600 --> 00:00:06.759 lessons learned in the development and introduction of closed loop 3 00:00:06.799 --> 00:00:10.480 systems from the twenty twenty four pod Partnership Opportunities and 4 00:00:10.519 --> 00:00:15.400 Drug Delivery Conference. For more information about the pod conference, editorials, podcasts, 5 00:00:15.480 --> 00:00:19.440 or webcasts, please visit Drug desh Delivery dot org. Thank 6 00:00:19.480 --> 00:00:20.760 you and enjoy the podcast. 7 00:00:21.320 --> 00:00:23.920 Good afternoon, everybody. Thank you for sticking around towards the 8 00:00:24.000 --> 00:00:26.280 end here. It's a privilege to be able to moderate 9 00:00:26.320 --> 00:00:29.640 this panel today on a topic very near to many 10 00:00:29.679 --> 00:00:32.039 of our careers and hearts on looking at closed loop 11 00:00:32.079 --> 00:00:37.000 systems across multiple therapeutic areas. Lessons learned. I'll introduce myself 12 00:00:37.039 --> 00:00:39.039 first and then ask my fellow panelists to do the same. 13 00:00:39.320 --> 00:00:43.439 Chris Kovalcik I lead this systems engineering organization within Abbott 14 00:00:43.439 --> 00:00:48.600 Diabetes Care, responsible for the development and commercialization of the 15 00:00:48.759 --> 00:00:52.039 entire portfolio of diabetes care products, including the Freestyle Every 16 00:00:52.079 --> 00:00:56.679 Glucose monitoring system and their associated cloud and mobile application services. 17 00:00:58.159 --> 00:00:59.159 Hi. Stephen Russell. 18 00:00:59.240 --> 00:01:03.039 I'm an associated professor at Harvard Medical School and over 19 00:01:03.039 --> 00:01:05.760 the last few years, the chief medical officer of Beta Bionics, 20 00:01:05.799 --> 00:01:09.680 which is a company that makes an automated insulin delivery system. 21 00:01:11.640 --> 00:01:11.760 Hi. 22 00:01:11.959 --> 00:01:17.079 Am Hindley Pinkson from the bio Innovation Hub nov Ive 23 00:01:17.280 --> 00:01:18.159 Externally Innovation. 24 00:01:20.200 --> 00:01:24.000 Hey Ben Lane from Key Technologies. I'm VP of Product Development. 25 00:01:24.560 --> 00:01:26.599 We've been around for a little over twenty five years, 26 00:01:26.640 --> 00:01:30.359 and much of that time we've been developing diagnostics and 27 00:01:30.480 --> 00:01:33.159 drug delivery devices, so we've been in this market for 28 00:01:33.239 --> 00:01:33.840 quite some time. 29 00:01:35.359 --> 00:01:38.480 Hi, my name is Louiterritor. I'm a pH Kennedy at 30 00:01:38.519 --> 00:01:41.560 Harvard Medical School and MIT working with Bob Linger and 31 00:01:41.680 --> 00:01:45.439 Geo Traversal on this closed loop drug delivery device, which 32 00:01:45.439 --> 00:01:46.480 we'll be talking about shortly. 33 00:01:47.640 --> 00:01:50.040 Okay, So to start us off to some common background. 34 00:01:50.040 --> 00:01:52.719 When we talk about a closed loop system, you generally 35 00:01:52.760 --> 00:01:55.079 need three or four ingredients to do so. Need to 36 00:01:55.079 --> 00:01:58.560 be able to measure a metric or variable, diagnose a 37 00:01:58.599 --> 00:02:01.879 dose or a therapy, deliver that dose, and you also 38 00:02:01.879 --> 00:02:03.040 need a drug to be able to do that in 39 00:02:03.120 --> 00:02:07.359 some cases. So if we look at what therapeutic ecosystem 40 00:02:07.480 --> 00:02:10.240 has been at the forefront of closed loop space for 41 00:02:10.319 --> 00:02:12.879 the last twenty years or so, it's been diabetes. So 42 00:02:13.000 --> 00:02:16.080 first question I'd like to ask doctor Russell, why has 43 00:02:16.159 --> 00:02:20.199 diabetes been so successful in terms of not only development 44 00:02:20.199 --> 00:02:22.960 of closed loop systems, but commercial uptake and getting it 45 00:02:22.960 --> 00:02:25.000 out to patients compared to other therapy areas. 46 00:02:26.080 --> 00:02:28.560 Sure, I think the reason that diabetes has been at 47 00:02:28.560 --> 00:02:30.319 the forefront is, first of all, you mentioned we have 48 00:02:30.400 --> 00:02:35.759 to measure something. The physiologically important variable in diabetes is glucose, 49 00:02:35.759 --> 00:02:40.120 blood glucose, and fortunately blood glucose is in equilibrium with 50 00:02:40.159 --> 00:02:42.879 interstitial fluid glucose, which then can be measured in a 51 00:02:42.919 --> 00:02:47.879 minimally invasive way with continuous glucose monitoring devices, and they've 52 00:02:48.360 --> 00:02:52.120 gotten progressively more accurate and more reliable, to the point 53 00:02:52.159 --> 00:02:57.319 that now the accuracy is excellent. The next piece is 54 00:02:57.360 --> 00:03:02.520 that for delivery, we have insulin, which can also be 55 00:03:02.599 --> 00:03:04.080 delivered subcutaneously. 56 00:03:04.120 --> 00:03:05.240 It's absorbed very well. 57 00:03:05.280 --> 00:03:10.560 The pharmacokinetics are pretty good for the ultra rapid insulin analogs, 58 00:03:11.360 --> 00:03:14.560 and so that means that the control loop isn't too long. 59 00:03:14.840 --> 00:03:17.840 I mean, if you measure something and then deliver something, 60 00:03:18.120 --> 00:03:20.159 but then the drug that you deliver doesn't have an 61 00:03:20.159 --> 00:03:24.039 effect for a day, that's not going to work. Fortunately, 62 00:03:24.840 --> 00:03:29.840 insulin works within reaches peak and blood within an hour 63 00:03:29.960 --> 00:03:33.680 or so, and you can get a relatively short control loop. 64 00:03:33.719 --> 00:03:37.120 And then the reason it's had uptake is that it's 65 00:03:37.159 --> 00:03:39.719 really hard to control glucose by yourself as a patient. 66 00:03:40.840 --> 00:03:42.560 Diabetes is completely unique, and. 67 00:03:42.520 --> 00:03:45.520 That we've got this really powerful, really dangerous drug, insulin, 68 00:03:46.120 --> 00:03:48.599 and then we tell patients to figure out how much 69 00:03:48.639 --> 00:03:51.560 of it to give themselves multiple times a day, which 70 00:03:51.599 --> 00:03:55.520 is absolutely crazy and doesn't happen anywhere else in medicine. 71 00:03:55.680 --> 00:03:58.919 And so there was a real unmet need for changing 72 00:03:58.960 --> 00:04:03.439 that us the the development of closed loop systems and 73 00:04:03.520 --> 00:04:09.840 their uptake once they were developed, I think, yeah, so I. 74 00:04:09.840 --> 00:04:15.639 Would just echo that that the burden of treating yourself 75 00:04:16.120 --> 00:04:22.399 every day and adjusting many times throughout the day is 76 00:04:22.920 --> 00:04:28.000 really big. And and then maybe also that the way 77 00:04:28.079 --> 00:04:30.759 that it came about that we have closed loop today, 78 00:04:31.319 --> 00:04:34.040 it didn't came in one day. We tried back in 79 00:04:34.319 --> 00:04:37.480 the seventies where there's something you carried on your back. 80 00:04:38.360 --> 00:04:42.360 And and then you say, insulin came out and was 81 00:04:42.399 --> 00:04:47.279 a business in itself. Then the pins were there, pumps 82 00:04:47.319 --> 00:04:50.399 came out, was a business in the themself. And first 83 00:04:50.519 --> 00:04:53.600 the ten years after the CDMs came out, we were 84 00:04:53.600 --> 00:04:58.000 able to get it approved as a closed loop system. 85 00:04:58.319 --> 00:05:01.600 So going along those lines with the success of diabetes 86 00:05:01.639 --> 00:05:03.720 and closed loop on it. I'll start with you, what 87 00:05:03.800 --> 00:05:07.560 are some of the areas we've seen limitations or areas 88 00:05:07.560 --> 00:05:10.839 for improvement before we segue into other therapy areas. 89 00:05:12.439 --> 00:05:15.680 Okay, yeah, So then I think if first I will 90 00:05:16.079 --> 00:05:19.639 just trying to skitch out where we are today, and 91 00:05:19.680 --> 00:05:22.040 I think Steve did a bit of that with the 92 00:05:23.519 --> 00:05:25.360 With the you would say that it starts with that 93 00:05:25.399 --> 00:05:28.519 we are giving a bolus in from from the pump, 94 00:05:29.399 --> 00:05:32.120 and then when do you see that effect on the 95 00:05:32.160 --> 00:05:35.399 CTM since you need to wait around one and a 96 00:05:35.439 --> 00:05:38.839 half hour before it has been throughout the system, so 97 00:05:38.879 --> 00:05:44.079 there is a big time delay in the system. It works, 98 00:05:44.439 --> 00:05:48.600 and people are adjusting the meal habits and shows so 99 00:05:48.639 --> 00:05:53.160 they don't get too much fluctuation there. But then the 100 00:05:53.360 --> 00:05:57.319 in the we say then what could come that could 101 00:05:57.399 --> 00:06:00.040 change this? I think the first thing would be to 102 00:06:00.079 --> 00:06:03.480 get the time to lay down and and the biggest 103 00:06:03.480 --> 00:06:09.079 element is the insulin. And right now we have a 104 00:06:09.560 --> 00:06:16.720 dedicated insulin in in clinical trials and that that will 105 00:06:16.759 --> 00:06:21.399 work so fast that they will not be available in 106 00:06:21.480 --> 00:06:25.560 pins because they might give a hypoglycemia before you're finished 107 00:06:25.560 --> 00:06:29.160 with your meal. So so we can cut down a 108 00:06:29.160 --> 00:06:32.399 lot of time delay on the insulin. Then I would 109 00:06:32.399 --> 00:06:36.480 say on the pump side, we have an infusion set. 110 00:06:37.000 --> 00:06:40.680 It sits on for three to seven days. CTMs can 111 00:06:40.720 --> 00:06:45.959 sit on for fourteen days. Maybe you could picture that 112 00:06:46.079 --> 00:06:51.360 the infusion set could reach the same level as CDM. 113 00:06:51.759 --> 00:06:55.079 On the CTM sensors, you see a trend on moving 114 00:06:55.120 --> 00:07:00.879 from subcutis interstitial liquid measurement and some of the new 115 00:07:00.879 --> 00:07:06.040 ones going into and when you go into dermal you 116 00:07:06.040 --> 00:07:11.199 will gain five to ten minutes more in the reduced 117 00:07:11.199 --> 00:07:15.759 time delay. And then you can say, if you look 118 00:07:18.879 --> 00:07:22.639 not on the system but the alternatives, then there's cell 119 00:07:22.759 --> 00:07:26.920 therapy making Bezza cells and putting them in the pocket 120 00:07:26.959 --> 00:07:31.240 in the in the body, and there's a glucose sensitive 121 00:07:31.279 --> 00:07:32.759 incident on its way. 122 00:07:34.279 --> 00:07:36.560 So if we consider everyone sitting in this room, the 123 00:07:36.600 --> 00:07:39.639 majority of us work for organizations that work across a 124 00:07:39.720 --> 00:07:43.759 variety of therapy ecosystems. So I'd like to segue into 125 00:07:43.839 --> 00:07:48.439 to lewis what are if you had to garner a guess, 126 00:07:48.480 --> 00:07:52.319 what's the next therapy that's right for closed loop infiltration 127 00:07:52.560 --> 00:07:53.639 outside of diabetes. 128 00:07:54.480 --> 00:07:57.639 Definitely, I'd say in chology is a space that really 129 00:07:57.720 --> 00:08:00.680 is just prime to have close loop therapies start to 130 00:08:00.680 --> 00:08:04.120 be implemented. So I'm sure many of us have experienced 131 00:08:04.199 --> 00:08:07.000 someone in our life receiving chemotherapy, but they don't think 132 00:08:07.040 --> 00:08:10.000 many of us know is how they are dose. So 133 00:08:10.199 --> 00:08:13.040 chemotherapies have a very narrow therapeutic window, as many of 134 00:08:13.120 --> 00:08:17.879 us likely know. They work by killing cells through just 135 00:08:18.040 --> 00:08:19.959 kind of like means that would also kill healthy cells 136 00:08:20.000 --> 00:08:22.959 as well. But amazingly, the way that they're dose right 137 00:08:23.000 --> 00:08:26.040 now is on the body service area basis. And what 138 00:08:26.079 --> 00:08:28.319 that means is if you have Lebron James six nine 139 00:08:28.319 --> 00:08:31.360 two hundred and five two hundred and fifty pounds and 140 00:08:31.480 --> 00:08:31.879 happy the. 141 00:08:31.920 --> 00:08:34.120 Dwarf, if Happy the Dwarf was four six. 142 00:08:33.960 --> 00:08:36.600 Five hundred pounds, that'd get the same amount of chemotherapy. 143 00:08:37.080 --> 00:08:39.639 And the reason for that is the basis that they're 144 00:08:39.639 --> 00:08:43.000 doc on is using ideal body service area that comes 145 00:08:43.000 --> 00:08:44.720 from this equation from nineteen sixteen. 146 00:08:45.159 --> 00:08:46.320 So these two cousins to. 147 00:08:46.360 --> 00:08:49.200 Boy and to Boy, they empirically fit data to nine people. 148 00:08:49.480 --> 00:08:52.120 They took height and weight and body surface area and 149 00:08:52.159 --> 00:08:54.960 empirically fit this equation to it. And that's the standard 150 00:08:55.000 --> 00:08:57.960 of care today for figuring out how to dose patients 151 00:08:57.960 --> 00:09:00.279 with chemotherapy across the world that the data fire were 152 00:09:00.519 --> 00:09:03.480 in many other centers. So it really seems like oncology, 153 00:09:03.679 --> 00:09:06.399 just given the nature of the cytotoxicity of these drugs 154 00:09:06.399 --> 00:09:09.840 and just the center of characters being in the state 155 00:09:09.879 --> 00:09:11.759 where it's using this equation from one hundred years ago, 156 00:09:11.879 --> 00:09:15.440 or an abbreviated version of the pharma that was driving 157 00:09:15.440 --> 00:09:18.440 in nineteen seventy one when calculators weren't around, so it 158 00:09:18.480 --> 00:09:20.919 was a much easier way to get to BSA, but 159 00:09:20.960 --> 00:09:23.360 it was based on the Debois and Dubois parmula. So 160 00:09:23.519 --> 00:09:25.840 I'd say for those reasons, and the fact that the 161 00:09:25.879 --> 00:09:28.080 patient's generally in an a fusion care center, so you 162 00:09:28.159 --> 00:09:30.519 have the infusion pump puck directly up to them, so 163 00:09:30.600 --> 00:09:32.799 you have a way that you could modulate DELS to 164 00:09:33.559 --> 00:09:36.080 keep the concentration of drug within the therapeutic window. Really 165 00:09:36.399 --> 00:09:38.480 makes oncology a very interesting space. 166 00:09:40.879 --> 00:09:45.000 Yeah, it's interesting to think about these different time constants. 167 00:09:45.080 --> 00:09:48.720 You know, diabetes is a very very long time constant, 168 00:09:49.000 --> 00:09:51.600 sensors in there for a couple of weeks, whereas what 169 00:09:51.639 --> 00:09:54.679 you're talking about is more more acute. Acute maybe the 170 00:09:54.720 --> 00:09:57.360 wrong word but very short time caused. And there's plenty 171 00:09:57.399 --> 00:10:00.759 of other applications where you know that's time constant is 172 00:10:00.840 --> 00:10:03.879 on the treatment windows on the order of hours and 173 00:10:03.919 --> 00:10:09.720 not you know, days, weeks, years. 174 00:10:07.720 --> 00:10:11.080 Right, intermittent in that case, whereas somebody with type one 175 00:10:11.120 --> 00:10:15.039 diabetes has to be under insulin treatment for the entire 176 00:10:15.080 --> 00:10:18.960 rest of their lives. So whatever system you come up 177 00:10:19.000 --> 00:10:25.759 with has to be wearable and easily usable, and something 178 00:10:25.799 --> 00:10:30.679 that somebody can doesn't create more burden than it reduces. 179 00:10:31.759 --> 00:10:34.559 So going off that thread, the last panel talked a 180 00:10:34.559 --> 00:10:37.840 lot about considering the user and the development of these systems. 181 00:10:37.879 --> 00:10:40.879 So if we think across different therapy areas, the user 182 00:10:40.919 --> 00:10:43.759 plays a different role, right, So we talk about diabetes, 183 00:10:44.120 --> 00:10:48.000 the user is very intensely aware and often more educated 184 00:10:48.000 --> 00:10:50.120 on the technology than some of the people that develop 185 00:10:50.200 --> 00:10:53.600 the systems. If we think about other therapy areas like 186 00:10:53.679 --> 00:10:57.600 neurodegenerative or on cology, like you mentioned, open question to 187 00:10:57.600 --> 00:10:59.840 the panel, how do you see the role of these 188 00:11:00.080 --> 00:11:04.159 user playing in the different close loop applications across these 189 00:11:04.320 --> 00:11:06.120 therapy areas well. 190 00:11:06.159 --> 00:11:08.360 One thing I think is that we're trying to reduce 191 00:11:08.399 --> 00:11:10.960 the role of the user and Type one so. 192 00:11:10.879 --> 00:11:11.759 The first. 193 00:11:13.000 --> 00:11:17.279 Automated insulin delivery technologies are so called hybrid systems, so 194 00:11:17.320 --> 00:11:21.679 they modulate basil insulin. You need both basil and bolus insulin. 195 00:11:22.080 --> 00:11:26.360 Basil dealing with the basil insulin needs like overnight, and 196 00:11:26.399 --> 00:11:30.559 then bowl is dealing with meals and so forth. The 197 00:11:30.600 --> 00:11:34.279 systems typically manage the basil part and then the user 198 00:11:34.360 --> 00:11:39.000 is responsible for the bowls part. Our system, the islet 199 00:11:39.120 --> 00:11:41.240 is designed to take over one hundred percent of the 200 00:11:41.240 --> 00:11:45.320 insulin dosing and reduce the need for the user to 201 00:11:45.360 --> 00:11:48.120 get involved. And what we're trying to solve there is 202 00:11:48.120 --> 00:11:50.559 that only twenty percent of people with type one are 203 00:11:50.600 --> 00:11:53.080 able to maintain the kind of glucose control they're supposed 204 00:11:53.080 --> 00:11:58.320 to do because people with really good quantitative skills, really 205 00:11:58.320 --> 00:12:04.320 good attention to detail, so forth, people with great executive 206 00:12:04.320 --> 00:12:07.799 function they do fine. Everyone else doesn't. So taking the 207 00:12:07.879 --> 00:12:11.120 user out of the loop more and more is the 208 00:12:11.159 --> 00:12:13.360 direction we're trying to move in for diabetes. 209 00:12:16.039 --> 00:12:20.399 What about a therapy area such as Alzheimer's where the 210 00:12:20.879 --> 00:12:25.240 user could be the person with cognitive impairment or a caregiver. 211 00:12:26.480 --> 00:12:29.320 Anybody want to comment on, how do you see closeup 212 00:12:29.360 --> 00:12:30.679 playing in the Alzheimer's space. 213 00:12:31.919 --> 00:12:35.320 Yeah, I mean that's a super challenging patient population, right, 214 00:12:35.360 --> 00:12:40.600 I mean, diabetes has this massive patient population. I think, 215 00:12:40.720 --> 00:12:42.559 you know, we've done a very good job with the 216 00:12:42.639 --> 00:12:46.679 vast majority of that group. But there's certain are sub 217 00:12:46.919 --> 00:12:55.799 certainly are subgroups pediatric, you know, cognitive issues, dexterity issues 218 00:12:55.919 --> 00:13:02.399 where managing the treatment but then also just applying the pump, 219 00:13:02.600 --> 00:13:06.440 applying the sensor becomes very challenging for that patient group 220 00:13:06.480 --> 00:13:10.039 and there's definitely room for improvement there. 221 00:13:12.200 --> 00:13:16.440 The question with things like you know, neurodegenerative diseases is 222 00:13:16.480 --> 00:13:21.960 what to measure, right. I'm interested in Parkinson's because my 223 00:13:22.000 --> 00:13:26.159 mother suffers from that and she has to take this 224 00:13:26.240 --> 00:13:30.879 complicated regimen of multiple doses. V just I guess recently 225 00:13:30.919 --> 00:13:34.720 got approval for doodopa, which is an sebt Q infusion, 226 00:13:35.320 --> 00:13:37.440 so that seems very familiar to me. 227 00:13:37.480 --> 00:13:38.360 In the insulin space. 228 00:13:38.399 --> 00:13:42.080 You can infuse this drug supultaneously maintain steady levels. But 229 00:13:42.120 --> 00:13:43.440 if you were going to try and turn that into 230 00:13:43.480 --> 00:13:46.919 a closed loop system, what would you measure? You know, 231 00:13:46.960 --> 00:13:54.159 would you measure interstitial dopamine That's not really where it functions, right, 232 00:13:54.679 --> 00:13:58.759 So would you measure tremor maybe you could do something 233 00:13:58.840 --> 00:14:02.639 like that. I think that becomes the challenge for these 234 00:14:02.679 --> 00:14:04.480 other fields. 235 00:14:07.480 --> 00:14:11.200 You could say that if it's not a fully closed loop, 236 00:14:11.279 --> 00:14:14.960 but just some of the components, like using the CDM 237 00:14:15.039 --> 00:14:19.440 for for other for other things, then I think that 238 00:14:19.480 --> 00:14:22.440 the that the we have tried out to use a 239 00:14:22.559 --> 00:14:29.879 CDM for tight trading once weekly insulin to figure out 240 00:14:30.120 --> 00:14:33.639 quite fast where to go and then go up in 241 00:14:33.679 --> 00:14:39.559 a few steps. Yeah, so really long acting components getting 242 00:14:39.600 --> 00:14:44.240 them to the right level fast. Uh. And one other 243 00:14:45.120 --> 00:14:48.679 element could be to use the CTM sensus for anti 244 00:14:48.720 --> 00:14:49.679 obesity treatment. 245 00:14:52.120 --> 00:14:55.279 So segueing to lessons learned, one of the areas we've 246 00:14:55.320 --> 00:14:58.240 talked about so far as the readiness of the technology. 247 00:14:58.440 --> 00:15:00.279 So back to the diabetes space. 248 00:15:00.320 --> 00:15:02.240 A lot of the technologies used to do any of 249 00:15:02.240 --> 00:15:06.200 these aspects of closed loop development have been readily available 250 00:15:06.279 --> 00:15:09.279 for the last twenty years. But even still, if you 251 00:15:09.320 --> 00:15:13.279 look at the companies playing in this game, very few 252 00:15:13.399 --> 00:15:17.039 if any, develop all of the technology all internally and 253 00:15:17.200 --> 00:15:21.200 requires a lot of partnership. So if Ben, I'll go 254 00:15:21.240 --> 00:15:25.840 to you, if we look at focusing on improving technology 255 00:15:25.840 --> 00:15:28.759 in these other areas, what are some of the advices 256 00:15:28.840 --> 00:15:32.200 or lessons learned that you've seen that helps not only 257 00:15:32.279 --> 00:15:34.879 develop this technology, but be able to partner effectively to 258 00:15:34.919 --> 00:15:37.120 get these solutions out to patients for other areas. 259 00:15:37.480 --> 00:15:38.600 Yeah, that's a great question. 260 00:15:38.879 --> 00:15:44.559 I think, you know, the collaboration of all the partners 261 00:15:45.000 --> 00:15:50.639 that are involved in this ecosystem, it's a complicated beast 262 00:15:50.799 --> 00:15:56.200 raight and the ability to rapidly develop and deploy a 263 00:15:56.279 --> 00:16:02.639 system depends on early engagement between all those parties. So 264 00:16:02.679 --> 00:16:05.919 you're developing a holistic system from the beginning as opposed 265 00:16:05.960 --> 00:16:08.759 to disparate development that then gets tied together. 266 00:16:08.480 --> 00:16:09.279 At the end. 267 00:16:10.120 --> 00:16:13.360 And it's a very difficult challenge. We see it all 268 00:16:13.399 --> 00:16:16.879 the time in diagnostics where the you know, the assay 269 00:16:17.000 --> 00:16:20.039 is developed and then the consumables developed and the instruments developed, 270 00:16:20.039 --> 00:16:26.159 and there's not that holistic from the beginning viewpoint, and I, 271 00:16:26.480 --> 00:16:28.559 you know, I don't have a lot of great answers there. 272 00:16:28.559 --> 00:16:33.080 It's very challenging because very often the pharma company is 273 00:16:33.120 --> 00:16:35.399 not in the in the hardware space. 274 00:16:36.559 --> 00:16:38.679 And the drug delivery. 275 00:16:38.240 --> 00:16:41.960 Company is not in the diagnostic space, and so tying 276 00:16:42.039 --> 00:16:47.960 all that together early to develop that holistic, efficient system 277 00:16:48.120 --> 00:16:49.840 is particularly challenging. 278 00:16:50.559 --> 00:16:53.960 The regulators can help a lot though that's another place 279 00:16:53.960 --> 00:16:54.840 we haven't discussed that. 280 00:16:54.840 --> 00:16:55.840 We had an advantage in. 281 00:16:55.840 --> 00:17:00.360 The diabetes space because the FDA created an it's this 282 00:17:01.399 --> 00:17:06.880 five ten K pathway for closed loop systems, and they 283 00:17:07.160 --> 00:17:13.079 created something called interoperable CGM, an ICGM with so it's 284 00:17:13.119 --> 00:17:16.559 a five to ten K with special controls and essentially 285 00:17:17.079 --> 00:17:20.799 if it could communicate with one of the devices in 286 00:17:20.839 --> 00:17:26.039 the x ecosystem and if it met certain accuracy criteria, 287 00:17:26.559 --> 00:17:29.640 then you could get this ICGM status. And as a 288 00:17:29.680 --> 00:17:32.720 company making a closed loop device, we are able to 289 00:17:32.799 --> 00:17:37.640 now do the study with one ICGM and then substitute 290 00:17:37.640 --> 00:17:42.200 another ICGM into our system without a regulatory filing. We 291 00:17:42.279 --> 00:17:45.920 just did a letter to file, so that really accelerated 292 00:17:45.960 --> 00:17:50.279 the whole process tremendously. You know, we launched with one CGM, 293 00:17:50.920 --> 00:17:53.960 we got the spec for another CGM, and launched four 294 00:17:54.000 --> 00:17:57.079 months later with a second CGM, and then we got 295 00:17:57.400 --> 00:17:59.920 the spec for a third and then launched a number 296 00:17:59.920 --> 00:18:02.039 of months later for that, and now we're we've got 297 00:18:02.079 --> 00:18:04.720 three CGM sensors that are all available, so it's user 298 00:18:04.799 --> 00:18:08.839 choice that wouldn't have been possible without the FDA stepping 299 00:18:08.880 --> 00:18:10.720 in and creating that regulatory framework. 300 00:18:13.400 --> 00:18:18.079 You could also say that by going through a partner's 301 00:18:18.200 --> 00:18:22.440 you open up a free, free competition and the BIST, 302 00:18:22.480 --> 00:18:26.559 the pump company can can pick the BIST CTM company 303 00:18:27.240 --> 00:18:30.160 and I and you get it even bitter system than 304 00:18:30.240 --> 00:18:32.440 if they try to do it internal. 305 00:18:33.799 --> 00:18:37.240 Yeah, this is an interesting space because you have companies 306 00:18:37.240 --> 00:18:40.880 who are partners and competitors at the same time, sometimes 307 00:18:40.880 --> 00:18:46.039 even on the same product. Switching to another technology question 308 00:18:46.240 --> 00:18:49.480 with this for you, So you mentioned oncology, and in 309 00:18:49.559 --> 00:18:53.160 terms of companion diagnostics, to measure the metric you're proposing 310 00:18:53.240 --> 00:18:58.039 requires a sophisticated technology in the clinic to be able 311 00:18:58.039 --> 00:19:02.480 to measure. Do you see start with oncology, Do you 312 00:19:02.519 --> 00:19:05.519 see that becoming a low cost product eventually? And what 313 00:19:05.559 --> 00:19:08.000 do you think would it take to get away from 314 00:19:08.039 --> 00:19:12.920 a diagnostic machine to measure the variable versus a wearable What. 315 00:19:12.880 --> 00:19:13.759 Are your thoughts there? 316 00:19:14.160 --> 00:19:18.160 Yeah, absolutely, So for context, we've developed this closed loop 317 00:19:18.240 --> 00:19:21.720 drug delivery system to control of the concentration of chemotherapy 318 00:19:21.799 --> 00:19:24.119 and we've shown it in vivo we published it earlier 319 00:19:24.160 --> 00:19:26.880 this year. So in the system, we draw a blood 320 00:19:26.920 --> 00:19:29.720 from the animal or eventually a patient and then we 321 00:19:29.880 --> 00:19:32.599 do this raptive the blood preprocessing step to then put 322 00:19:32.599 --> 00:19:35.839 it onto a high performance to liquid chromatography MasSpec or 323 00:19:35.960 --> 00:19:39.720 HBOCMS system, which has been as many of the people 324 00:19:39.759 --> 00:19:41.640 in this audience likely know, a gold standard by the 325 00:19:41.759 --> 00:19:45.240 FDA to determine the concentration of drug for many many 326 00:19:45.279 --> 00:19:48.480 different clinical trials over the years. So we really wanted 327 00:19:48.480 --> 00:19:51.000 to design the sensor or the overall system around the 328 00:19:51.039 --> 00:19:54.319 sensor because of the development and the trust and to 329 00:19:54.400 --> 00:19:56.200 the points that we're mentioned earlier, the fact that you 330 00:19:56.240 --> 00:19:57.880 really need this sensor, and that's one of the things 331 00:19:57.880 --> 00:20:00.759 that really helped in the diabete space to enable closer 332 00:20:00.839 --> 00:20:04.000 the control. So we designed this overall system around LCMS, 333 00:20:04.440 --> 00:20:07.240 and then the loop gets closed by taking that concentration 334 00:20:07.319 --> 00:20:10.759 reading and put it into the control algorithm. So with that, 335 00:20:10.759 --> 00:20:12.799 that's one of the major questions we always get is 336 00:20:12.960 --> 00:20:15.880 LCMS is very expensive. The high end ones that you'd 337 00:20:15.960 --> 00:20:17.960 likely want in the clinic are just shy of about 338 00:20:18.000 --> 00:20:21.559 a million dollars, So the upfront cost is large, But 339 00:20:21.640 --> 00:20:23.759 when you start thinking about the lifetime of these types 340 00:20:23.799 --> 00:20:26.599 of devices, they'd likely last with good maintenance on the 341 00:20:26.680 --> 00:20:29.279 order of about a decade. You can imagine you can 342 00:20:29.319 --> 00:20:31.720 do about two maybe three patients a day with the 343 00:20:31.759 --> 00:20:34.920 system comes down to about one thousand uses over a year, 344 00:20:35.039 --> 00:20:38.799 ten thousand over a decade, So the cost per patient 345 00:20:38.960 --> 00:20:41.079 is approximately one hundred dollars if you work it out 346 00:20:41.319 --> 00:20:43.839 according to that way. Of course, there's many other variables 347 00:20:43.880 --> 00:20:46.240 that go into account with it. You'd have to have 348 00:20:46.359 --> 00:20:48.799 personal cost, but the cost of the system isn't as 349 00:20:48.920 --> 00:20:52.359 large as you'd initially think, and there's likely if this 350 00:20:52.440 --> 00:20:54.319 system were ever to reach it to the clinic, they'd 351 00:20:54.319 --> 00:20:57.359 likely be work continuing to bring the cost of the 352 00:20:57.480 --> 00:21:02.640 LCMS device down. So definitely opportunity i'd say is the 353 00:21:03.000 --> 00:21:05.960 ability to make low cost LCMS devices is definitely something 354 00:21:06.000 --> 00:21:09.640 that's interesting, and that's just one of many different types 355 00:21:09.680 --> 00:21:11.559 of approaches you get take for the censor, But we 356 00:21:11.640 --> 00:21:13.920 really decided to focus on that just because it is 357 00:21:15.079 --> 00:21:17.799 very well trusted, able to be applied to multiple different drugs, 358 00:21:17.839 --> 00:21:20.000 and there's allowed of us to develop this system and 359 00:21:20.519 --> 00:21:22.720 apply it to a chemotherapy space. 360 00:21:23.400 --> 00:21:24.960 You also have to think about the value. 361 00:21:25.039 --> 00:21:29.200 So in the diabetes space, you know, these devices are 362 00:21:29.200 --> 00:21:31.279 not nearly as expensive as that, but there are a 363 00:21:31.359 --> 00:21:35.799 lot of people because each person needs one and multiple 364 00:21:35.839 --> 00:21:38.799 over their lifetime. Usually, but we're reducing the risk of 365 00:21:38.839 --> 00:21:41.880 long term complications, and you, I believe would be reducing 366 00:21:41.880 --> 00:21:46.960 the risk of chemotherapy related complications because of overdosing or 367 00:21:47.200 --> 00:21:51.000 inadequate treatment of a cancer from underdosing. So I think 368 00:21:51.000 --> 00:21:52.880 you can easily make the argument that a one hundred 369 00:21:52.920 --> 00:21:58.000 dollars is worth the reduction to an insurance company is 370 00:21:58.720 --> 00:22:01.559 worth the reduction of those those complications. 371 00:22:02.000 --> 00:22:02.279 Yeah. 372 00:22:02.319 --> 00:22:06.519 Absolutely, There's been this additional approach that's been developed therapeutic 373 00:22:06.559 --> 00:22:08.680 drug monitoring, where you take the concentration of the end 374 00:22:08.680 --> 00:22:11.119 of one around of chemotherapy and then don't suggest for 375 00:22:11.119 --> 00:22:13.599 the next round of chemotherapy. And even with that, which 376 00:22:13.599 --> 00:22:15.640 if you think about it, that's the closed system. It's 377 00:22:15.640 --> 00:22:17.720 a sampling rate in the case of five few of 378 00:22:17.759 --> 00:22:20.640 once per two weeks. It's a very basic control algorithm 379 00:22:20.640 --> 00:22:24.200 that's normally for five few. The clinical trials I'm aware 380 00:22:24.240 --> 00:22:26.279 of that have been done, it's a rule spase algorithm, 381 00:22:26.359 --> 00:22:28.559 so if you're a certain percent above, you decrease by 382 00:22:28.759 --> 00:22:31.599 x percent of the dose. So even within those trials, 383 00:22:31.640 --> 00:22:34.759 they've shown benefit in terms of tox and efficacy. So 384 00:22:35.119 --> 00:22:37.599 I completely agree with you, and in the paper we 385 00:22:37.599 --> 00:22:39.720 put out, we did some preliminary analysis on that with 386 00:22:39.759 --> 00:22:43.240 certain assumptions of how much benefit we could apply based 387 00:22:43.240 --> 00:22:45.559 on those TDM studies, and it does when you take 388 00:22:45.559 --> 00:22:48.039 everything into account, does appear that it could be cost effective, 389 00:22:48.079 --> 00:22:51.119 even given the high costs involved. 390 00:22:53.440 --> 00:22:55.119 An area like to go into a little bit is 391 00:22:55.160 --> 00:22:59.960 around access. So when the first hybrid closed loop technology 392 00:23:00.160 --> 00:23:03.359 is launched in the diabetes space, if you purely look 393 00:23:03.400 --> 00:23:06.920 at the physics and the technology, it's a no brainer 394 00:23:07.039 --> 00:23:12.039 that every single person with diabetes would therapeutically benefit from 395 00:23:12.039 --> 00:23:15.519 this system. However, if you look at the percent of 396 00:23:15.599 --> 00:23:19.640 the population of persons with diabetes that are on such 397 00:23:19.680 --> 00:23:23.680 a system is incredibly low, a single digit percent. How 398 00:23:23.720 --> 00:23:28.079 do we increase access to these technologies by building patient 399 00:23:28.079 --> 00:23:30.920 trust not only a diabetes space, but in other therapeutic 400 00:23:31.039 --> 00:23:33.920 areas where the concept of a closed loop system would 401 00:23:33.920 --> 00:23:36.880