WEBVTT 1 00:00:00.160 --> 00:00:03.680 Welcome to Farmer Talk Radio. This podcast is focused on 2 00:00:03.759 --> 00:00:07.879 biomateial implants to reduce patient burden and improve adherence from 3 00:00:07.919 --> 00:00:12.160 the twenty twenty four pod Partnership Opportunities and Drug Delivery Conference. 4 00:00:12.480 --> 00:00:17.280 For more information on the pod conference, editorials, podcasts, or webcasts, 5 00:00:17.600 --> 00:00:20.719 please visit Drug dash Delivery dot org. Thank you and 6 00:00:20.839 --> 00:00:21.760 enjoy the podcast. 7 00:00:23.079 --> 00:00:26.760 Our topic today is biomaterial implants for reducing patient burden 8 00:00:26.800 --> 00:00:32.719 and improving adherence. I'm joined by four fellow colleagues and 9 00:00:32.799 --> 00:00:38.200 the drug delivery and the device field and let's get started. 10 00:00:38.240 --> 00:00:39.719 So there was. 11 00:00:39.719 --> 00:00:43.920 A similar session earlier on a similar topic, but I 12 00:00:43.920 --> 00:00:47.880 think we'll have a different perspective perhaps, But before we start, 13 00:00:47.920 --> 00:00:51.240 maybe we'd just give a general introduction to what we 14 00:00:51.320 --> 00:00:56.679 mean by biomaterials and implants. So there's a biomaterial in 15 00:00:56.719 --> 00:01:00.479 this setting is basically any material that's coming in contact body. 16 00:01:01.280 --> 00:01:07.000 Of course, for a therapeutic application, we have special requirements biocompatibility, 17 00:01:07.319 --> 00:01:11.560 maybe bioorotability, but an implant in the general sense could 18 00:01:11.599 --> 00:01:18.480 be any parental depot that's giving a long sustained release 19 00:01:18.519 --> 00:01:20.719 of an API. But we also have sort of a 20 00:01:20.760 --> 00:01:24.239 classical definition of an implant. I'd like to sort of 21 00:01:25.159 --> 00:01:28.239 ask the panel premier perspective, what do you think of 22 00:01:28.280 --> 00:01:31.719 when you think of an implant versus a other type 23 00:01:31.760 --> 00:01:33.159 of long acting injectable. 24 00:01:35.000 --> 00:01:40.719 So I'm Jamie Sean with Pfizer, I head the Global 25 00:01:40.719 --> 00:01:45.439 Biopharmaceutics Group for introduction. Yeah, so I think I told 26 00:01:45.480 --> 00:01:48.920 the group at one time that from my classical perspective, 27 00:01:51.079 --> 00:01:54.480 something which can be injected is a depot injection or 28 00:01:54.480 --> 00:01:58.560 a long long acting injection, while something which actually has 29 00:01:58.599 --> 00:02:01.920 to be inserted or could be you are too implant, 30 00:02:01.959 --> 00:02:06.120 it is an implant. However, that definition is getting blurred, 31 00:02:06.280 --> 00:02:09.000 and I think the USB and the regularty Agency is 32 00:02:09.080 --> 00:02:12.759 kind of don't differentiate it that way. However, there is 33 00:02:12.800 --> 00:02:15.680 an impact in terms of how we define implant as 34 00:02:15.680 --> 00:02:18.039 to how it is going to be designed and developed, 35 00:02:18.080 --> 00:02:18.560 and we can. 36 00:02:18.439 --> 00:02:19.319 Talk about that later. 37 00:02:20.919 --> 00:02:22.199 The other thoughts. 38 00:02:23.199 --> 00:02:27.719 Yeah, I think classically we start with that to that point, 39 00:02:27.840 --> 00:02:32.520 jam In, you know, an injectable with a fixed geometry 40 00:02:32.840 --> 00:02:36.000 is something that would be defined as an implant. But 41 00:02:36.080 --> 00:02:39.199 if you expand it and taking into consideration the USB 42 00:02:39.360 --> 00:02:44.319 definition is it's injected, it's probably localized at a certain site, 43 00:02:44.960 --> 00:02:47.719 and from that site, it's doing a sustained delivery of 44 00:02:47.840 --> 00:02:51.840 an active agent. Not necessarily the active agent is being 45 00:02:52.120 --> 00:02:55.800 a you know, a control release, but it's some other 46 00:02:55.840 --> 00:02:59.240 mechanism that is helping you to control the release or 47 00:02:59.240 --> 00:03:01.919 control the solution of that drug and getting into the 48 00:03:01.960 --> 00:03:05.520 systemic circulation. And in the broader definition, that's how it 49 00:03:05.599 --> 00:03:10.360 falls into an implant classification, even if it is injected 50 00:03:10.800 --> 00:03:13.960 and not inserted. So that's what we were talking about 51 00:03:13.960 --> 00:03:16.599 earlier as well, and. 52 00:03:16.800 --> 00:03:20.719 In the title of our panel discussion is why in 53 00:03:20.759 --> 00:03:22.800 the definition of why we want to actually use a 54 00:03:22.800 --> 00:03:26.120 bio material implant, so for reducing patient burden and improving 55 00:03:26.120 --> 00:03:28.840 the adherence. I'm curious, Aileen Eric, if maybe you can 56 00:03:29.199 --> 00:03:34.759 give some examples of use cases that are justifying the 57 00:03:34.840 --> 00:03:37.439 use of biomterial implants in your work. 58 00:03:38.280 --> 00:03:41.400 Sure I can go first. My name is Eileen Sadly. 59 00:03:41.520 --> 00:03:45.199 I am a senior scientist that APPY. I work on 60 00:03:45.560 --> 00:03:51.039 a drug delivery and combination product. Just for introduction, The 61 00:03:51.080 --> 00:03:57.080 reason we use implant is for localized and control drug delivery, 62 00:03:57.639 --> 00:04:02.000 especially for hard to reach tissues in the body such 63 00:04:02.000 --> 00:04:07.759 as retinal diseases, as well as oncology applications. That makes 64 00:04:07.759 --> 00:04:09.039 the impluse super important. 65 00:04:11.840 --> 00:04:15.000 Uh. Hello, I'm Eric Almquist. I'm the co founder and 66 00:04:15.120 --> 00:04:18.639 CEO of Pendent Biosciences. I have a little bit different 67 00:04:18.639 --> 00:04:23.000 perspective from everybody else up here. We are the drug 68 00:04:23.040 --> 00:04:27.639 delivery company that works with my colleagues here and as clients. 69 00:04:28.360 --> 00:04:31.680 So you know, from our perspective, we really are driven 70 00:04:31.720 --> 00:04:37.199 by our clients' needs. So you know, from from most 71 00:04:37.240 --> 00:04:41.680 of my experience and creating these delivery devices, it's really 72 00:04:41.759 --> 00:04:46.279 driven by taking and existing therapeutic that's already commercialized or 73 00:04:46.319 --> 00:04:49.560 on the market and really improving the patient experience or 74 00:04:49.600 --> 00:04:55.199 the provider experience by by delivering a a more efficacious 75 00:04:55.240 --> 00:04:57.000 dose or longer lasting dose. 76 00:04:58.759 --> 00:05:03.600 I have one example or use case or an area 77 00:05:03.720 --> 00:05:06.199 where actually it kind of really kind of showed like 78 00:05:06.319 --> 00:05:10.319 where implants can significantly benefit, and this is an ocular 79 00:05:10.519 --> 00:05:13.720 drug delivery to back of the eye. I think some 80 00:05:13.800 --> 00:05:15.879 of you might know that at one time there were 81 00:05:15.920 --> 00:05:18.879 really no drug products for the back of the eye, 82 00:05:19.040 --> 00:05:21.879 and at that time, if you had an infection, they 83 00:05:21.920 --> 00:05:25.519 would basically give a systemic antibiotic or oral antibiotic, but 84 00:05:25.800 --> 00:05:28.600 very small fraction of that goes to the back of 85 00:05:28.639 --> 00:05:32.759 the eye during the AIDS epidemic. There were this CMB 86 00:05:32.920 --> 00:05:35.600 infections in the back of the eye and folks were 87 00:05:35.600 --> 00:05:38.959 losing eyesight. At that time, they were using some of 88 00:05:39.040 --> 00:05:42.600 the anti viral agents systemically, but a company developed an 89 00:05:42.600 --> 00:05:45.560 implant which would be implanted into the eye into the 90 00:05:45.639 --> 00:05:48.839 victory as known as vitrosert. But it was a fairly 91 00:05:48.920 --> 00:05:53.399 large implant, and slowly that company developed another next generation, Reticert, 92 00:05:53.480 --> 00:05:57.079 and then Medidior, and as it kind of evolved, it 93 00:05:57.160 --> 00:05:59.879 became which was an implant which was to be inserted 94 00:05:59.920 --> 00:06:03.920 into something which can be injected. So the definition gets blood. 95 00:06:04.079 --> 00:06:06.839 But why do we do that? That's because you can't 96 00:06:06.839 --> 00:06:10.720 really do frequent injections into the eye. The best you 97 00:06:10.759 --> 00:06:12.759 can do is once a month, but you can't go 98 00:06:12.839 --> 00:06:14.800 as So the idea was to kind of have an 99 00:06:14.800 --> 00:06:17.160 implant which can deliver the drug for more than a 100 00:06:17.240 --> 00:06:19.759 year a year to three years, and so that's the 101 00:06:19.879 --> 00:06:23.399 driver one of the really good example of why implants 102 00:06:23.399 --> 00:06:25.800 are needed for certain conditions. 103 00:06:27.000 --> 00:06:30.720 Yeah, I think I've also worked in a molecular drug delivery, 104 00:06:30.800 --> 00:06:34.040 and I think going from that example, one of the 105 00:06:34.079 --> 00:06:39.120 most beautiful examples I've seen is this refillable port delivery 106 00:06:39.160 --> 00:06:45.360 system that was commercialized by roch Genentech, and it's interesting 107 00:06:45.439 --> 00:06:48.240 reading all the papers about that and seeing the presentations, 108 00:06:48.319 --> 00:06:52.040 like how many iterations and how many problems there were 109 00:06:52.079 --> 00:06:54.759 to solve. And I think that gets to a topic 110 00:06:54.839 --> 00:06:58.040 that we've discussed prior to this panel, which is that 111 00:06:58.439 --> 00:07:03.560 developing these long acting implants or injectables can be very complicated, 112 00:07:03.759 --> 00:07:07.120 and anyone who's worked in that field sort of sympathizes 113 00:07:07.160 --> 00:07:12.439 with each other about that process. And I'm curious to 114 00:07:12.480 --> 00:07:17.040 hear from the panel what is it that's complicated or 115 00:07:17.079 --> 00:07:21.959 difficult about developing a long acting biomaterial implant. 116 00:07:24.240 --> 00:07:29.319 So I think classically, from an implant perspective, you don't 117 00:07:29.319 --> 00:07:32.160 want the implant to be intrusive or physically to beg 118 00:07:32.439 --> 00:07:36.079 so that means that implant, when you design an implant, 119 00:07:36.360 --> 00:07:40.000 the drug has to be very potent. It's better also 120 00:07:40.079 --> 00:07:42.959 if the drug is a long half life, and so 121 00:07:43.079 --> 00:07:46.879 I think portent to the drug is important. Secondly, finding 122 00:07:46.879 --> 00:07:49.319 the right material for the implant and the right design 123 00:07:49.360 --> 00:07:52.240 of the implant asually, to be honest, there are very 124 00:07:52.240 --> 00:07:54.399 few materials which can be used in implants, and we 125 00:07:54.439 --> 00:07:57.600 can talk about that later, So that's kind of thing. Secondly, 126 00:07:57.639 --> 00:08:00.240 it's sort of a design not just the formulation but 127 00:08:00.319 --> 00:08:04.319 also the design of the implant, which requires bioengineering principles. 128 00:08:04.720 --> 00:08:08.360 So it's a very challenging you know, design from a 129 00:08:08.720 --> 00:08:11.800 first in man implant is well, it's almost has to 130 00:08:11.839 --> 00:08:13.279 be commercializable. 131 00:08:16.199 --> 00:08:19.519 I think, you know, maybe it can relate to everybody. 132 00:08:19.560 --> 00:08:23.079 So because you guys are here at the last you know, 133 00:08:24.040 --> 00:08:27.879 panel discussion, and the biggest trait that it needs is 134 00:08:27.879 --> 00:08:33.360 the patients and these are long acting delivery systems and 135 00:08:33.399 --> 00:08:36.720 it needs a lot of patients during the development. So 136 00:08:36.759 --> 00:08:39.120 the design factory is definitely one of them, which is 137 00:08:39.360 --> 00:08:43.120 you know, highly challenging because you're looking into the drug factors, 138 00:08:43.639 --> 00:08:46.919 you're looking into the excpient or the biomterials that you're using. 139 00:08:48.039 --> 00:08:50.919 And then the second part is the process that comes in, 140 00:08:50.960 --> 00:08:54.519 and the process is equally challenging, and the patience comes 141 00:08:54.519 --> 00:08:57.440 in because now you're looking at the clinical development of 142 00:08:57.480 --> 00:09:01.000 these implants and then you're going to test the patients 143 00:09:01.039 --> 00:09:04.759 of the organization as a whole, because you're not looking 144 00:09:04.799 --> 00:09:08.240 at just uh, the developability of that, but you're looking 145 00:09:08.279 --> 00:09:10.960 at the clinical outcomes coming from that and how long 146 00:09:11.519 --> 00:09:16.480 an organization can can sustain in that competitive space to 147 00:09:17.200 --> 00:09:19.200 you know, be patient with you and say, okay, keep 148 00:09:19.240 --> 00:09:22.240 doing what you're doing, even though it takes long time. 149 00:09:22.320 --> 00:09:24.639 There are a lot of values behind it from from 150 00:09:24.720 --> 00:09:28.600 the market perspective, but the patients is a key thing 151 00:09:28.639 --> 00:09:31.840 that many times we see a lot of challenges and difficulties. 152 00:09:31.240 --> 00:09:32.399 In these developments. 153 00:09:34.879 --> 00:09:37.200 Yeah, just to echoat, I think one of the most 154 00:09:37.240 --> 00:09:42.440 important problem we face, usually especially for chronic diseases like 155 00:09:42.919 --> 00:09:47.720 inflammation in the eye retinal diseases is basically balancing between 156 00:09:47.759 --> 00:09:51.720 the release profile and the material degradation. You don't want 157 00:09:51.720 --> 00:09:56.200 to have and people get multiple injection for chronic diseases, 158 00:09:56.279 --> 00:09:59.600 you don't want you want to factor that in. You 159 00:09:59.600 --> 00:10:03.279 don't want to have multiple implants in their eye. That 160 00:10:03.360 --> 00:10:08.600 becomes a burden. And secondly, as it was also mentioned, 161 00:10:08.720 --> 00:10:12.559 is that it takes a long time for making an implant, 162 00:10:12.600 --> 00:10:15.879 and especially degradeable implant, one of the requirements is to 163 00:10:16.000 --> 00:10:19.799 show the degradation. And these days with competitive landscape, if 164 00:10:19.840 --> 00:10:21.840 you want to have like six months or one year 165 00:10:22.279 --> 00:10:26.240 even delivery, you should show that degradation, which usually takes 166 00:10:26.279 --> 00:10:30.960 longer than the release profile. So that makes the timeline 167 00:10:31.559 --> 00:10:36.879 very long, and that also makes you wonder about the 168 00:10:36.919 --> 00:10:37.919 competitive market. 169 00:10:39.960 --> 00:10:43.039 So from the other side of the table, by the 170 00:10:43.080 --> 00:10:46.480 time these guys come to us, that means they've already 171 00:10:46.519 --> 00:10:51.799 tried the traditional technologies, the plgas, the standard materials that 172 00:10:51.840 --> 00:10:52.919 everybody is very familiar with. 173 00:10:53.000 --> 00:10:54.120 So we get all the hard stuff. 174 00:10:55.279 --> 00:11:00.879 So we're subject subjected to the market shifts the interests 175 00:11:00.879 --> 00:11:05.039 of our clients. You know, it was maybe small molecules 176 00:11:05.080 --> 00:11:06.679 ten years ago, fifteen years ago. 177 00:11:06.519 --> 00:11:07.480 Now it's biologics. 178 00:11:08.000 --> 00:11:13.799 So our challenge is to fit find the solution for 179 00:11:13.840 --> 00:11:17.440 the target product profile we're presented with and make something 180 00:11:17.519 --> 00:11:21.360 work in a time frame that's that's reasonable for our 181 00:11:21.399 --> 00:11:22.639 clients to continue moving forward. 182 00:11:22.679 --> 00:11:24.960 Otherwise the market shifts again. 183 00:11:27.759 --> 00:11:30.679 So given how long it can take to develop some 184 00:11:30.720 --> 00:11:34.639 of these products, do you have any suggestions from your 185 00:11:34.639 --> 00:11:39.000 own experience on what you could do to streamline, Like 186 00:11:39.159 --> 00:11:41.159 what should you do? What should you do early on 187 00:11:41.320 --> 00:11:44.200 because you don't get as many shots on goal when 188 00:11:44.279 --> 00:11:49.720 you're cycle the time is multiple months. What has been 189 00:11:49.759 --> 00:11:52.159 successful in your experience or in hindsight. 190 00:11:53.600 --> 00:11:56.200 This really I mean, I think there's no single part, 191 00:11:56.360 --> 00:11:59.879 but I think ideally you know you what you want 192 00:11:59.879 --> 00:12:02.559 to take into the first in human or first in 193 00:12:02.639 --> 00:12:10.120 patient study is sort of a commercializable truck product because 194 00:12:10.159 --> 00:12:12.200 in this case you won't be able to establish bio 195 00:12:12.200 --> 00:12:16.039 equivalents that easily because if it's a local implant, if 196 00:12:16.080 --> 00:12:18.679 it's a systemic implant, yes you can do bi equivalents, 197 00:12:18.759 --> 00:12:23.720 but it's risking right because there's high variability. So whatever 198 00:12:24.320 --> 00:12:26.279 you need to do in terms of design, in terms 199 00:12:26.320 --> 00:12:28.759 of pre clinical work, in terms of peak and safety, 200 00:12:28.840 --> 00:12:31.200 you want to do it in the right model, animal model, 201 00:12:32.159 --> 00:12:36.000 Get the right design, and then kind of make sure 202 00:12:36.039 --> 00:12:39.039 that you have good line of sight as to can 203 00:12:39.120 --> 00:12:42.159 you can you scale up the process, Is it going 204 00:12:42.200 --> 00:12:45.799 to be robust? Is it going to perform appropriately before 205 00:12:45.840 --> 00:12:48.960 phase one? Probably even the ideal you would want to 206 00:12:49.000 --> 00:12:51.399 wait for an oral solid I would wait till phase 207 00:12:51.440 --> 00:12:53.679 two be but in this case you will have to 208 00:12:53.720 --> 00:12:56.480 do it ahead of time. Now that's not well received 209 00:12:56.519 --> 00:12:58.879 by the asset team because they would want to go fast, 210 00:12:59.720 --> 00:13:01.480 and so that's where the challenge occurs. 211 00:13:04.159 --> 00:13:09.679 Yeah, I certainly echo that, and I think to Sean's 212 00:13:10.080 --> 00:13:13.840 to Erx's point as well. You know, the broader the 213 00:13:13.919 --> 00:13:17.200 TPP in the beginning, the better it is, because then 214 00:13:17.960 --> 00:13:21.799 the scientists and the development team has more room to 215 00:13:22.039 --> 00:13:24.320 come up with a narrower scope as they go, and 216 00:13:24.360 --> 00:13:27.440 this progress and all of these factors that Jamie just 217 00:13:27.559 --> 00:13:30.399 mentioned over the period of time, you would be narrowing 218 00:13:30.440 --> 00:13:34.360 it down as you go more closer towards the final product, 219 00:13:34.799 --> 00:13:35.960 but not necessarily. 220 00:13:36.679 --> 00:13:38.480 You know you're you're going to define. 221 00:13:38.480 --> 00:13:41.120 At that point, you probably have the definition and vision 222 00:13:41.200 --> 00:13:43.519 way ahead of your products. So even when you have 223 00:13:43.639 --> 00:13:47.000 your TPPS, you probably have the vision of the product 224 00:13:47.000 --> 00:13:49.360 that you want to deliver to a patient. So in 225 00:13:49.440 --> 00:13:53.200 terms of your final presentation, but in terms of that 226 00:13:53.320 --> 00:13:56.320 development pathway that you know, you go with the broader 227 00:13:56.360 --> 00:13:58.320 scope and then you kind of narrow it down as 228 00:13:58.360 --> 00:14:01.080 you go. And then next part of that is they're 229 00:14:01.120 --> 00:14:05.639 taking an incremental step of success and not jumping through 230 00:14:05.720 --> 00:14:10.120 because many times you see this that you know probably 231 00:14:10.200 --> 00:14:12.399 end up taking a bit more risk than it's required 232 00:14:12.960 --> 00:14:17.600 and then end up having a more challenging situation because 233 00:14:18.080 --> 00:14:20.360 you know there's a study which needs to be done 234 00:14:20.600 --> 00:14:23.519 from the feasibility point of view, but it's it's it's 235 00:14:23.559 --> 00:14:27.360 not must, it's good to have, but sometimes skipping something 236 00:14:27.440 --> 00:14:31.720 like that can become far more challenging down the line. 237 00:14:31.360 --> 00:14:35.559 So having that kind of very methodical approach in this 238 00:14:35.759 --> 00:14:38.919 overall development, going step by step, and then when you 239 00:14:39.000 --> 00:14:43.240 go from that translation from pre clinical to clinical, that 240 00:14:43.279 --> 00:14:46.919 would significantly improve the confidence of the product. And then 241 00:14:46.960 --> 00:14:49.360 that's how you probably see better success with that. 242 00:14:51.879 --> 00:14:53.919 Just to add to that, one thing that we learned 243 00:14:54.240 --> 00:14:59.120 along the way is, as you mentioned, also not only 244 00:14:59.159 --> 00:15:02.440 having the right animal model would help a lot showing efficacy, 245 00:15:02.559 --> 00:15:05.919 but also the right model for the adverse events, like 246 00:15:06.000 --> 00:15:11.320 even inducing them into animals and having the true exhaustive 247 00:15:11.480 --> 00:15:16.440 basically all the experiments that can be done to induce 248 00:15:16.480 --> 00:15:20.320 that and to see how that adverse event can first 249 00:15:20.440 --> 00:15:23.440 in the first place, show up even in the smallest 250 00:15:23.480 --> 00:15:28.639 number of patients, just to know about it and just 251 00:15:28.679 --> 00:15:31.360 to have an idea if that's going to be a 252 00:15:31.360 --> 00:15:32.279 problem later on. 253 00:15:34.200 --> 00:15:36.360 For us, it comes down to two things. 254 00:15:37.840 --> 00:15:41.320 We need very clear communication and direction from our partners. 255 00:15:42.240 --> 00:15:44.679 We are not the drug experts. We don't know as 256 00:15:44.759 --> 00:15:47.960 much about the API as you guys do. And any 257 00:15:48.000 --> 00:15:51.960 other thing, of course, is the financial support. You know, 258 00:15:52.200 --> 00:15:57.039 we we can move as quickly as our resources allow 259 00:15:57.200 --> 00:16:01.720 resources allow us to. So you know, we have many 260 00:16:01.720 --> 00:16:05.960 different options available to us, and you know we can 261 00:16:06.000 --> 00:16:07.000 go slower, go faster. 262 00:16:09.600 --> 00:16:15.200 So I'm curious what sort of gaps in biomaterial or 263 00:16:15.320 --> 00:16:20.320 implant or long acting injectbal technologies do you all see 264 00:16:21.240 --> 00:16:25.320 that leave you wanting more like that you would look 265 00:16:25.399 --> 00:16:29.679 for startups or other companies to be developing for your 266 00:16:29.720 --> 00:16:31.960 next project or your current project. 267 00:16:33.120 --> 00:16:35.000 Well, the one thing which comes to my mind is 268 00:16:35.039 --> 00:16:40.480 the material, the components of the implant, and you could 269 00:16:40.519 --> 00:16:44.519 classify them as metallic or the polymeric, right, And if 270 00:16:44.559 --> 00:16:49.519 you look at polymeric implants, either institute gel or the 271 00:16:49.559 --> 00:16:54.639 pre formed implant, PLG is kind of like the standard 272 00:16:54.919 --> 00:16:58.720 polymer which everybody uses because it's well characterized, safe, etc. 273 00:17:00.080 --> 00:17:02.399 And I remember that there were a lot of other 274 00:17:02.480 --> 00:17:09.160 polymers evaluated and has been studied, like caprolacton, polyarthesters, polynhydrites, 275 00:17:10.039 --> 00:17:13.039 but unfortunately none of those polymers have kind of reached 276 00:17:13.039 --> 00:17:15.200 the stage where they have become sort of like a 277 00:17:15.240 --> 00:17:19.079 standard alternate to PLGA. And so I think there is 278 00:17:19.119 --> 00:17:21.599 a gap in terms of having new biomaterials which are 279 00:17:21.640 --> 00:17:26.440 as safe compatible like PLGA, which perform as well. And 280 00:17:26.519 --> 00:17:30.000 PLGA is its own issues in terms of the diffusional release, 281 00:17:30.079 --> 00:17:33.279 the erosinal release, and not ability to control release as well, 282 00:17:34.559 --> 00:17:37.240 and for metallic implant also there are limited choices and 283 00:17:37.319 --> 00:17:40.200 limited companies which have the ability to do that. So 284 00:17:40.240 --> 00:17:42.839 I think those are the things which I think I 285 00:17:42.880 --> 00:17:45.200 see as one of the gap into the materials available. 286 00:17:47.599 --> 00:17:51.039 Yeah, I think PLGA came maybe in early eighties or 287 00:17:51.079 --> 00:17:53.720 even earlier than that. But after that, if you see 288 00:17:53.759 --> 00:17:58.400 any biodegraded polymer which is approved by the FDA for 289 00:17:58.559 --> 00:18:03.000 any pharmaceutical application is very less especially an injectable space 290 00:18:03.039 --> 00:18:07.039 if we talk uh and certainly I think that is 291 00:18:07.079 --> 00:18:11.759 one of the key challenges to have a suitable biocompatible 292 00:18:11.799 --> 00:18:15.599 material and if possible a biodegradable material for an implant delivery, 293 00:18:16.240 --> 00:18:19.680 that would definitely make it more appealing, especially for the pharma. 294 00:18:19.440 --> 00:18:21.599 Companies to go and try these things. 295 00:18:22.759 --> 00:18:25.440 One of the challenges possibly in that one is the 296 00:18:25.680 --> 00:18:32.440 excipient approval pathway from the regulatory agency can be you know, 297 00:18:32.480 --> 00:18:36.440 a chicken and egg kind of a situation, whether you 298 00:18:36.480 --> 00:18:38.119 know who would be the first one to go and 299 00:18:38.400 --> 00:18:41.799 then try that out and and do that. But there's 300 00:18:41.799 --> 00:18:44.039 a lesson or multiple lessons to be learned from a 301 00:18:44.079 --> 00:18:46.680 device side and a device industry, because they have been 302 00:18:46.759 --> 00:18:51.920 quite successful using different biocompatible materials metal or non metal UH. 303 00:18:51.960 --> 00:18:54.480 And I think some kind of a cross collaboration between 304 00:18:54.519 --> 00:18:56.839 a pharma company and a device company can be really 305 00:18:56.960 --> 00:19:00.880 helpful in that and in that space to come up 306 00:19:00.920 --> 00:19:06.039 with those injectable you know, implants and more suitable biomaterials 307 00:19:06.599 --> 00:19:09.960 to be used for this kind of application for drug delivery. 308 00:19:11.240 --> 00:19:14.759 Yes, material is definitely one of the biggest gap. There 309 00:19:14.839 --> 00:19:16.759 is only a handful of them that has been have 310 00:19:16.839 --> 00:19:21.079 being tested so far, and it's mainly p g A 311 00:19:21.279 --> 00:19:25.839 that people use in the industry. And also one of 312 00:19:25.880 --> 00:19:30.119 another bigger gap that I can mention is implants for 313 00:19:30.200 --> 00:19:35.519 biologics that it's very hard to develop, especially with the 314 00:19:35.559 --> 00:19:42.119 degradable implants, and that's another area of interest. If can 315 00:19:42.160 --> 00:19:46.480 be developed into degredible implants. 316 00:19:45.880 --> 00:19:47.839 Make them as a surprise. I'm going to say materials 317 00:19:47.839 --> 00:19:55.079 as well my shameless plug here for self promotion. You know, 318 00:19:55.119 --> 00:19:59.359 from from my experience UH independent, we have seen a 319 00:19:59.359 --> 00:20:05.400 significant s gift and the openness UH for our drug partners. 320 00:20:04.920 --> 00:20:08.279 To be interested in alternative materials. 321 00:20:09.119 --> 00:20:12.799 I think the interest in hydrophilics and large molecules is 322 00:20:13.160 --> 00:20:16.119 largely driven that. As much as we can twist and 323 00:20:16.160 --> 00:20:18.599 poke and prod PLGA. Sometimes it's just not going to 324 00:20:18.640 --> 00:20:21.279 work and UH and I and we do see a 325 00:20:21.359 --> 00:20:23.839 shift in the in the willingness of our partners to 326 00:20:23.839 --> 00:20:25.519 be open to new materials. 327 00:20:26.559 --> 00:20:30.119 And I second that maial new materials for formulation with 328 00:20:30.599 --> 00:20:33.880 biologics is something that we look a lot for as well, 329 00:20:35.279 --> 00:20:37.960 not only for compatibility with the biologic and giving the 330 00:20:37.960 --> 00:20:40.400 sustained or release profile you want, but also having the 331 00:20:40.440 --> 00:20:45.559 ability to potentially, you know, sterilize. How do you sterilize these? 332 00:20:45.640 --> 00:20:52.400 And you know, we we hate doing a septic manufacturing, 333 00:20:52.559 --> 00:20:55.480 but it's almost the only option if you're working with 334 00:20:55.480 --> 00:20:58.640 any sort of particulate or implant. So one thing I've 335 00:20:58.680 --> 00:21:02.839 always been on the lookout for are long acting solutions 336 00:21:02.880 --> 00:21:06.519 for biologics that are like an in situ, in situ 337 00:21:06.599 --> 00:21:10.960 forming depot that maybe you can sterile filter and UH 338 00:21:11.319 --> 00:21:16.440 and get the right balance of release no burst, long release, 339 00:21:16.519 --> 00:21:20.759 no burst, and good tolerability. So that's on my wish list. 340 00:21:21.119 --> 00:21:23.039 Reach reach out to me later if you have something 341 00:21:28.079 --> 00:21:31.480 in terms of yeah, what about what about like device 342 00:21:31.720 --> 00:21:38.119 like implantable devices sort of deep refillable depots. I mentioned 343 00:21:38.119 --> 00:21:42.799 that this this like a port. How about applying those 344 00:21:42.799 --> 00:21:46.279 to other tissues or other sort of devices that have 345 00:21:46.319 --> 00:21:49.960 a sort of smart, sort of mechanical release. Any have 346 00:21:50.039 --> 00:21:51.240 any of you looked at those. 347 00:21:52.599 --> 00:21:56.799 So my so I I haven't really worked directly with them, 348 00:21:56.839 --> 00:22:00.160 but I know that for ocular applications that have in 349 00:22:00.240 --> 00:22:04.519 several implants designed. One is the port system which you describe, 350 00:22:04.519 --> 00:22:07.079 which gene and Tech developed where you could refill it. 351 00:22:08.240 --> 00:22:10.680 There was another delivery system which was like a micro 352 00:22:11.599 --> 00:22:15.519 electrical mechanical system where you actually was electrically driven pump 353 00:22:15.599 --> 00:22:20.200 to pump the fluid into the vitreos. But also I've 354 00:22:20.240 --> 00:22:25.720 seen papers and some work on pumps for bringing delivery local, 355 00:22:25.880 --> 00:22:29.759 localized delivery to the parts of the brain. Those are 356 00:22:29.880 --> 00:22:31.519 very you know, unique examples. 357 00:22:32.000 --> 00:22:32.440 I haven't. 358 00:22:32.559 --> 00:22:35.599 I don't have experience working with them per se. 359 00:22:36.440 --> 00:22:39.480 Yeah, I think limited experience in that space. But but 360 00:22:39.880 --> 00:22:44.279 you're looking at instead of having a passive chemical based 361 00:22:44.279 --> 00:22:48.079 diffusion based system, we are looking at a physical stimuli 362 00:22:48.160 --> 00:22:51.960 coming in either an electrical uh, you know, signal or 363 00:22:52.000 --> 00:22:56.400 something like that. And I think there are a lot 364 00:22:56.440 --> 00:22:59.960 of you know, probably a couple of areas, the therapeutic areas, 365 00:23:00.079 --> 00:23:02.680 maybe the contraceptives is one of them, where we have 366 00:23:02.759 --> 00:23:07.759 seen some of those applications, especially with metallic implants. Hope 367 00:23:07.759 --> 00:23:09.359 to see a lot more on the type one and 368 00:23:09.400 --> 00:23:13.079 type two diabetes space. We have just had that amazing 369 00:23:13.119 --> 00:23:18.799 discussion right before this one, and seeing something in that regard, 370 00:23:18.839 --> 00:23:23.240 I think either I think, just continuing to that wishless 371 00:23:23.279 --> 00:23:27.279 part is if a metallic implant or a biocompatible implant 372 00:23:27.359 --> 00:23:31.400 is inserted and if it is refillable, then that that 373 00:23:31.559 --> 00:23:36.039 takes a lot of these design and then formulation challenges 374 00:23:36.079 --> 00:23:39.920 off the table and possibly it can provide a much 375 00:23:39.960 --> 00:23:40.720 longer delivery. 376 00:23:40.799 --> 00:23:43.480 So something to look for. 377 00:23:46.720 --> 00:23:50.000 We have about five minutes left. We could open the 378 00:23:50.240 --> 00:23:52.400 floor to the audience if anyone has any questions for 379 00:23:52.440 --> 00:23:52.880 the panel. 380 00:23:58.480 --> 00:24:03.519 Hi Stephen Russell, Chief clos Circuito Bionics. I think for me, 381 00:24:03.599 --> 00:24:06.319 it's pretty obvious if you have a localized delivery problem, 382 00:24:06.400 --> 00:24:08.839 why an implant would be a really good option. 383 00:24:09.000 --> 00:24:11.079 But for more systemic delivery. 384 00:24:11.119 --> 00:24:13.119 Now that we have so many drugs at least in 385 00:24:13.160 --> 00:24:16.240 my diabetes space, like GLP one agnes that are given weekly, 386 00:24:17.160 --> 00:24:19.480 and there was a recent failure of an implant to 387 00:24:19.519 --> 00:24:24.960 give a GLP one in tarsia that wasn't approved, what 388 00:24:25.079 --> 00:24:28.839 are the specific circumstances where you would want an implant 389 00:24:29.119 --> 00:24:32.559 to give a drug systemically as opposed to. 390 00:24:34.160 --> 00:24:34.599 Locally. 391 00:24:36.960 --> 00:24:39.440 Yeah, I think in my experience what I'm aware of 392 00:24:39.640 --> 00:24:42.559 is and systemic. All say it was primary to reduce 393 00:24:43.000 --> 00:24:47.000 patient burden, right adherence. One of the oldest implant is 394 00:24:47.000 --> 00:24:49.839 the zolax implant by Estra Zeneca, which is like a 395 00:24:49.960 --> 00:24:54.400 very small implant implanted using a broker. And then there 396 00:24:54.480 --> 00:24:57.039 was an implant being developed for prosted cancer where it 397 00:24:57.079 --> 00:25:00.000 was like a long duration I think duration is imported. 398 00:25:00.680 --> 00:25:03.319 At one time one could not have assumed that you 399 00:25:03.319 --> 00:25:05.400 could get a long acting in the injectable that will 400 00:25:05.400 --> 00:25:08.400 work for six months or provide sustained pKa profile for 401 00:25:08.480 --> 00:25:12.079