Pełna transkrypcja odcinka Matthew Oki O'Connor on Cyclodextrins & RAADfest 2025 Activist Panel

00:05:07.600 the years, but most in the last couple of decades. 65 00:05:07.639 --> 00:05:11.879 In medicine, they've been used mostly as delivery tools to 66 00:05:12.000 --> 00:05:16.839 deliver drugs as a part of drug formulations. But in 67 00:05:16.879 --> 00:05:20.000 twenty fifteen, the first cycled extro based drug was approved 68 00:05:21.079 --> 00:05:24.720 and it was acquired by merk It's now called Britian 69 00:05:25.079 --> 00:05:27.920 otherwise known as Sugarmaducks, and what it is is it's 70 00:05:27.920 --> 00:05:33.639 an antidote or reversal agent for a anesthesia agent, a paralytic, 71 00:05:33.959 --> 00:05:37.160 and so it grabs on to after when you're going 72 00:05:37.199 --> 00:05:40.680 to get surgery, you get dosed with the paralytics so 73 00:05:40.720 --> 00:05:44.720 that you don't move around during surgery, and then the 74 00:05:44.800 --> 00:05:49.439 anesthesiologist gives you Britian after they're done with the surgery, 75 00:05:49.639 --> 00:05:54.240 and the Britian sweeps through, grabs up all of the paralytic, 76 00:05:54.519 --> 00:05:59.160 pulls it out of your bloodstream and upee the Britian 77 00:05:59.279 --> 00:06:02.000 and the paralytic out and you wake up right away 78 00:06:02.120 --> 00:06:05.720 and you have no side effects from the paralytic and 79 00:06:08.759 --> 00:06:11.680 you're better off. Britain is a blockbuster drug. It's sold 80 00:06:11.720 --> 00:06:14.560 one point eight billion dollars last year, which is more 81 00:06:14.560 --> 00:06:19.879 than all of anesthesia combined. And this is the same 82 00:06:20.079 --> 00:06:24.160 type of approach that we want to take with our drugs, 83 00:06:24.279 --> 00:06:27.000 is to make things that are specific for a certain 84 00:06:27.000 --> 00:06:29.279 target that you don't need any more of. Right, you 85 00:06:29.279 --> 00:06:31.199 don't need any of that paralytic in your body after 86 00:06:31.240 --> 00:06:33.199 the surgery is done, so you just get rid of 87 00:06:33.240 --> 00:06:35.600 all of it, and the optimal amount of it to 88 00:06:35.680 --> 00:06:38.199 be in your body after the surgery is zero. So 89 00:06:38.279 --> 00:06:42.319 we developed this the cycled extra in technology, which is 90 00:06:42.360 --> 00:06:45.639 a dimerization technology where we stick to cycled extrints together. 91 00:06:45.759 --> 00:06:49.160 And that's pretty much the core of our intellectual property, 92 00:06:50.000 --> 00:06:53.240 which is the ability to encapsulate whatever it is that 93 00:06:53.279 --> 00:06:57.519 we build to target with one of our cyclic extrien dimers. 94 00:06:58.399 --> 00:07:02.879 And we've been granted serve patents in this area. So 95 00:07:03.319 --> 00:07:06.839 most of what I'll talk about today is targeting the 96 00:07:07.040 --> 00:07:10.959 oxidized form of cholesterol called seven keto cholesterol. I'll talk 97 00:07:10.959 --> 00:07:14.000 more about that in a minute. We're also working on 98 00:07:15.079 --> 00:07:18.839 targeting junk that accumulates in your eye with age and 99 00:07:19.000 --> 00:07:22.600 causes the major form of macular degeneration. We're also looking 100 00:07:22.639 --> 00:07:26.560 at nanoplastics, which is a good use case for our technology, 101 00:07:26.800 --> 00:07:30.240 as well as you know, some other things like an 102 00:07:30.279 --> 00:07:34.600 asusure reversal, which obviously there's there's many other anesthetics that 103 00:07:35.199 --> 00:07:40.319 we could build reversal agents for. So we started out 104 00:07:40.360 --> 00:07:45.000 pretty early on doing some pretty intense computational chemistry with 105 00:07:45.439 --> 00:07:50.000 cyclodextrins and as opposed to other groups, which there's many 106 00:07:50.040 --> 00:07:54.199 many groups doing computational chemistry simulations these days, not enough. 107 00:07:54.480 --> 00:07:58.959 I think it's a growing field and something that everyone 108 00:07:59.000 --> 00:08:02.879 needs to invest more in. But instead of going really 109 00:08:03.000 --> 00:08:07.240 general with computational chemistry or specializing in what most people 110 00:08:07.279 --> 00:08:10.920 specialize in, which is protein either protein protein interactions or 111 00:08:11.399 --> 00:08:19.560 ligand receptor ligand binding interactions, we focused on an only 112 00:08:19.639 --> 00:08:26.079 modeling cyclodextrins and their bonding with whatever target that we 113 00:08:26.120 --> 00:08:29.199 wanted to go after and we do increasing levels of 114 00:08:29.240 --> 00:08:33.720 sophistication of simulations until we get to the level where 115 00:08:33.720 --> 00:08:37.759 we can actually predict an affinity constant for a given 116 00:08:37.799 --> 00:08:41.559 target before we even synthesize it. And now what we're 117 00:08:41.600 --> 00:08:45.120 doing is layering on AI and machine learning so that 118 00:08:45.159 --> 00:08:48.159 we can actually take the human out of the process 119 00:08:48.200 --> 00:08:53.000 of designing the drug and let the AI iterate until 120 00:08:53.000 --> 00:08:57.039 it comes up with the ideal binding partner for whatever 121 00:08:57.279 --> 00:09:00.080 kind of molecular junk that we're trying to get rid of. 122 00:09:00.399 --> 00:09:02.480 So we did a lot of that to come up 123 00:09:02.519 --> 00:09:07.399 with our lead drug candidate, and then we synthesized a 124 00:09:07.480 --> 00:09:10.480 number of prototypes and iterated back and forth between the 125 00:09:10.559 --> 00:09:14.360 chemistry and the bench until we came up with our 126 00:09:14.360 --> 00:09:16.559 first drug that I'll tell you a little bit more 127 00:09:16.879 --> 00:09:19.360 about in a minute. But first of let me take 128 00:09:19.360 --> 00:09:25.200 a step back and talk about the free radical oxidation 129 00:09:25.360 --> 00:09:28.480 process that causes the kind of oxidized cholesterol that we're 130 00:09:28.480 --> 00:09:32.519 worried

about. So you've probably all heard free radicals. Free 131 00:09:32.559 --> 00:09:38.039 radicals have been around aging, medicine and biology for decades, 132 00:09:38.559 --> 00:09:42.799 and when you have an oxygen free radical, they can 133 00:09:42.840 --> 00:09:45.879 react with a lot of different molecules in negative ways. 134 00:09:45.879 --> 00:09:49.120 They can react with your DNA, with your mitochondria. When 135 00:09:49.120 --> 00:09:52.360 they react with regular cholesterol, which is pictured here in 136 00:09:52.480 --> 00:09:58.639 yellow in the middle, then you add a oxygen molecule on. Typically, 137 00:09:58.720 --> 00:10:01.919 so this is a non asomatic process. It's a random process, 138 00:10:01.960 --> 00:10:04.000 but it's not so random because more often than not, 139 00:10:04.720 --> 00:10:08.279 the chemistry prefers that it adds it in the seventh position, 140 00:10:08.559 --> 00:10:12.759 which means that you get seven ketocholesterol or seven KC, 141 00:10:13.200 --> 00:10:16.759 and I'll sort of use oxidizedcholesterol or a seven k 142 00:10:16.879 --> 00:10:21.600 C interchangeably in the rest of my presentation. And so 143 00:10:22.320 --> 00:10:27.879 oxidized cholesterol has been implicated in many aspects of aging, 144 00:10:28.919 --> 00:10:35.799 including aging in the eye and liver, aging and brain aging. 145 00:10:36.480 --> 00:10:39.120 Most of what I'm going to talk about today revolves 146 00:10:39.120 --> 00:10:44.159 around how it causes atheroscrosis in your blood vessels and 147 00:10:47.639 --> 00:10:50.919 how it does that. So this a lot of the 148 00:10:50.960 --> 00:10:55.200 concept behind cholesterol oxidation, how it happens and where it 149 00:10:55.279 --> 00:10:58.840 happens and when it happens, was worked out. A lot 150 00:10:58.879 --> 00:11:03.679 of it was working out in the nineties in vitro 151 00:11:03.960 --> 00:11:07.240 and in mice, but it's only in the last decade 152 00:11:07.240 --> 00:11:10.240 that we've started to see some really convincing evidence that 153 00:11:10.320 --> 00:11:15.159 oxidized cholesterol as well associated with cardiovascular disease, which with 154 00:11:15.279 --> 00:11:20.679 negative outcomes and with severity of disease. So there's a 155 00:11:20.679 --> 00:11:30.080 growing awareness of oxidized cholesterol's involvement in heart disease and atheroscrosis. 156 00:11:30.159 --> 00:11:33.080 So how does it do that? So when you get 157 00:11:33.120 --> 00:11:36.960 a alesion in your blood vessel wall, like a fatty 158 00:11:37.000 --> 00:11:41.960 streak that you start developing in your teenage years, a macrophage, 159 00:11:42.440 --> 00:11:45.679 part of your immune system, is supposed to come along 160 00:11:46.039 --> 00:11:51.559 and eat up that lesion. But when it runs into 161 00:11:51.759 --> 00:11:55.799 oxidized cholesterol, it can't digest it, and it can't it 162 00:11:55.840 --> 00:11:59.039 can't recycle it, it can't transport it back out into the bloodstream. Now, 163 00:11:59.080 --> 00:12:02.279 macrophage is a really good at recycling cholesterol. When they 164 00:12:02.320 --> 00:12:06.960 get regular cholesterol in the form of LDL, they take 165 00:12:07.000 --> 00:12:10.559 it apart and then repackage it into HDL and if 166 00:12:10.600 --> 00:12:13.759 they don't need it, and then return it back into 167 00:12:13.799 --> 00:12:15.919 circulation where it can go back to your liver for 168 00:12:16.000 --> 00:12:20.600 recycling back into the rest of the body where you 169 00:12:20.679 --> 00:12:24.440 might need more cholesterol. But with the oxidized forms of cholesterol, 170 00:12:24.600 --> 00:12:28.399 it can't do that. It can't do the reverse cholesterol transport, 171 00:12:28.720 --> 00:12:30.600 and so it just eats more and more of it. 172 00:12:30.720 --> 00:12:35.200 And this is the oxidized cholesterol as highly toxic and 173 00:12:35.720 --> 00:12:41.279 it causes the macrophage to start sequestering lipid and balloon 174 00:12:41.399 --> 00:12:45.600 up into something called the foam cell. And foam cells 175 00:12:45.639 --> 00:12:48.320 are these big blobby cells. They're kind of LIKEX and 176 00:12:48.440 --> 00:12:54.320 essence cells. But it's not caused by by the over 177 00:12:54.360 --> 00:12:57.840 division like with fibroblasts or something like you might have 178 00:12:57.879 --> 00:13:04.000 heard of, but it's caused by toxicity from things like oxidizedcholesterol. 179 00:13:04.600 --> 00:13:08.360 And foam cells build plaque. They are the driver of 180 00:13:08.600 --> 00:13:12.240 the mass of the plaque accumulation that you get, and 181 00:13:12.279 --> 00:13:17.960 it's an early and continuous stage in the plaque building process. 182 00:13:18.240 --> 00:13:21.200 What we wanted to do was ask ourselves, could we 183 00:13:21.240 --> 00:13:26.600 design a drug to specifically bind the common oxidized form 184 00:13:26.639 --> 00:13:30.759 of cholesterol, could we remove it from cells and tissues, 185 00:13:30.799 --> 00:13:36.600 and could removing that reverse the foam cell phenotype and 186 00:13:37.639 --> 00:13:42.679 potentially rescue atheroscrosis. So we built this drug, which we're 187 00:13:42.720 --> 00:13:46.440 calling udp zeror zero three, which we trained first computationally 188 00:13:46.600 --> 00:13:52.600 and then synthetically to prefer binding oxidized cholesterol and to 189 00:13:52.720 --> 00:13:57.320 ignore regular cholesterol, which you need to survive. And so 190 00:13:57.440 --> 00:14:02.879 we built this first drug and it has a very 191 00:14:02.919 --> 00:14:07.440 high affinity for the oxidized form of cholesterol and it 192 00:14:07.519 --> 00:14:11.919 leaves regular cholesterol alone. And we've done a great deal 193 00:14:11.960 --> 00:14:17.679 of work to characterize this drug and get it ready 194 00:14:19.320 --> 00:14:24.600 to be a drug. So first up here at the top, 195 00:14:24.720 --> 00:14:29.440

you have macrophages, just normal healthy macrophages grown, and then 196 00:14:29.480 --> 00:14:31.600 you give them a little bit of oxidized cholesterol and 197 00:14:31.639 --> 00:14:35.960 they bloon up into nasty looking foam cells. And then 198 00:14:36.000 --> 00:14:40.000 when we give our drug, they turn back into healthy 199 00:14:40.639 --> 00:14:49.279 macrophages without those blobby lipids in their in their cytosols. 200 00:14:49.720 --> 00:14:52.000 And your quantification of that here. 201 00:14:51.960 --> 00:14:53.840 So if you go back for a moment, I just 202 00:14:53.919 --> 00:14:59.759 want to see the quantities here. So it's ten micromolar 203 00:15:00.000 --> 00:15:01.080 sevn ketocholesterol. 204 00:15:01.240 --> 00:15:05.320 Yes, yeah, in this particular case. We've done it many 205 00:15:05.320 --> 00:15:09.240 different permutations of this, many different ways, and you can 206 00:15:09.279 --> 00:15:12.759 see how how that's working here. And so that's just 207 00:15:12.919 --> 00:15:16.879 how the macrophages look. How they look better, They look younger, right, 208 00:15:17.000 --> 00:15:19.480 they were nasty and old looking. But do they go 209 00:15:19.600 --> 00:15:22.000 back to doing their job? And the answer is yes. 210 00:15:22.240 --> 00:15:26.240 If you poison them with the oxidized cholesterol, their ability 211 00:15:26.279 --> 00:15:30.120 to eat, their ability to do phagocytosis drops, and then 212 00:15:31.559 --> 00:15:37.519 we give them our drug. The phagocytic capabilities come back 213 00:15:39.039 --> 00:15:43.000 multiple different ways with both human and mouse cells that 214 00:15:43.039 --> 00:15:47.200 we did this with. Perhaps more importantly I mentioned earlier 215 00:15:47.440 --> 00:15:50.759 reverse cholesterol transport, and that's a big part of the 216 00:15:50.879 --> 00:15:54.639 job of the macrophages in your blood vessels is to recycle, 217 00:15:54.840 --> 00:15:57.720 is to get rid of the excess cholesterol. But when 218 00:15:57.759 --> 00:16:01.759 you give them oxidized cholesterol, like over here on the left, 219 00:16:02.240 --> 00:16:07.679 the reverse cholesterol transport activity goes down to almost zero. 220 00:16:08.519 --> 00:16:13.919 And then when you give our drug, just very briefly 221 00:16:13.960 --> 00:16:16.960 for a short amount of time, it goes back up 222 00:16:17.440 --> 00:16:23.360 quite significantly, which we think means that our drug is 223 00:16:23.399 --> 00:16:26.759 restoring the ability the macrovisions to do their job not 224 00:16:26.840 --> 00:16:33.320 just in eating, but also in metabolizing cholesterol transporting cholesterol. 225 00:16:34.519 --> 00:16:41.960 And that's a pretty key aspect of atheroscrosis. So then 226 00:16:42.000 --> 00:16:44.600 we went through and did a good amount of characterization 227 00:16:44.679 --> 00:16:46.799 of the phenomenon and looked at gene expression. And I'll 228 00:16:46.840 --> 00:16:50.919 just show

a few examples from our recent publication on this. 229 00:16:51.639 --> 00:16:54.519 One is the CD forty seven, which is being targeted 230 00:16:54.519 --> 00:17:01.279 by a competitor of ours with a therapeutic antibody, which 231 00:17:01.960 --> 00:17:05.039 is kind of like in a tumor where the tumor 232 00:17:05.759 --> 00:17:09.000 evades the immune system. The foam cells do the same thing, 233 00:17:09.160 --> 00:17:11.920 so they turn up this don't eat me signal called 234 00:17:12.000 --> 00:17:15.920 CD forty seven. And what we've shown is that our 235 00:17:17.319 --> 00:17:22.319 treatment with our drug brings that back down a bit, 236 00:17:23.079 --> 00:17:25.519 so that the cells should be able to be cleared, 237 00:17:25.920 --> 00:17:27.839 the foam cells should be able to be cleared by 238 00:17:27.839 --> 00:17:33.680 other macrophages. Another, various aspects of lipid transport get done 239 00:17:33.759 --> 00:17:37.279 regulated and then go back to normal when we treat 240 00:17:37.319 --> 00:17:43.759 with our drug, and and and then various other aspects 241 00:17:43.960 --> 00:17:52.279 of inflammation of scavenging genes that are either upregulated or 242 00:17:52.319 --> 00:17:56.400 downregulated in response to the insult, which is the oxidized cholesterol, 243 00:17:56.799 --> 00:18:03.880 and then get reverted variously by treatment with our drug. 244 00:18:04.319 --> 00:18:07.680 Out of the weeds a little bit. What happens to 245 00:18:08.279 --> 00:18:13.119 animals when you give them our drug, Well, it's it's 246 00:18:13.160 --> 00:18:18.799 it's still early days with really fully investigating this, but 247 00:18:18.920 --> 00:18:21.640 this is the most exciting data that I think. I 248 00:18:21.640 --> 00:18:27.319 think generally that rodent models of cardiovascar disease of atheroscorosis 249 00:18:27.480 --> 00:18:36.720 are are pretty artificial and unrealistic, and so I don't 250 00:18:37.079 --> 00:18:39.799 really like them and I don't like working in them. 251 00:18:40.279 --> 00:18:45.680 But in in normal healthy rats, if you give them 252 00:18:45.680 --> 00:18:48.799 our drug, our drug is designed to be cleared very 253 00:18:48.839 --> 00:18:52.240 quickly and to be cleared through the urine. And that's 254 00:18:52.279 --> 00:18:54.599 exactly what we see. I'm not showing the data here, 255 00:18:55.160 --> 00:18:58.920 but actually when we dose with our drug, we see 256 00:18:58.960 --> 00:19:01.200 the target of our drug, wich is the oxidized olesterol 257 00:19:01.240 --> 00:19:03.319 coming out in the urine. And we see it coming 258 00:19:03.319 --> 00:19:05.880 out in the same time scale as we see our 259 00:19:05.960 --> 00:19:09.680 drug being excreted in the urine. And so this suggests 260 00:19:09.799 --> 00:19:12.799 that our drug is doing its job, and it's doing 261 00:19:12.880 --> 00:19:16.759 it very fast. And so the the animals are are 262 00:19:16.799 --> 00:19:21.839 peeing out their their oxidized cholesterol within a couple of 263 00:19:21.839 --> 00:19:24.480 hours of administration of the drug. 264 00:19:26.319 --> 00:19:26.440 Uh. 265 00:19:26.559 --> 00:19:28.680 And so this, this story that I just told you, 266 00:19:28.880 --> 00:19:33.759 was just recently published in the journal athos Crosis. And 267 00:19:33.759 --> 00:19:36.680 I should add in here that we just a professor 268 00:19:36.680 --> 00:19:41.200 in the field, without talking to us about it, wrote 269 00:19:41.200 --> 00:19:44.279 a nice commentary about our paper, and that was just 270 00:19:44.359 --> 00:19:51.799 published this past week. So we wanted to turn this 271 00:19:51.920 --> 00:19:55.240 into a clinical stage drunk, so we worked on the 272 00:19:55.359 --> 00:19:58.359 chemistry and the manufacturing. We scaled the process to kilogram 273 00:19:58.440 --> 00:20:03.599 scale manufacturing, We made large scale batches, we put it 274 00:20:03.640 --> 00:20:07.759 into single use sterile files. We had many meetings with 275 00:20:08.039 --> 00:20:12.200 regulators in many countries in the UK, in the US 276 00:20:12.319 --> 00:20:18.440 and in Australia. And then earlier this year we launched 277 00:20:18.519 --> 00:20:24.119 our Phase one clinical trial in Australia. And I'll tell 278 00:20:24.160 --> 00:20:27.599 you more about that in a minute, but first here's 279 00:20:28.079 --> 00:20:31.160 the leadership of our team, me and Mike Cope, co 280 00:20:31.240 --> 00:20:36.480 founders the company, Noah Rosenberg, the chief medical officer, and 281 00:20:36.599 --> 00:20:42.079 the clinical advisory board that he recruited to to help 282 00:20:42.200 --> 00:20:47.720 us turn our drug into into something that could go 283 00:20:47.839 --> 00:20:52.480 into people. So PK. Shaw was the main guy who 284 00:20:52.519 --> 00:20:56.920 dissected in the nineteen nineties the cholesterol oxidation process. And 285 00:20:56.960 --> 00:21:03.759 Steve Nichols is argue, the world's expert on how blaque 286 00:21:03.759 --> 00:21:06.680 is built. He's got about I think eight hundred publications 287 00:21:06.680 --> 00:21:10.839 on the subject and he is leading our clinical trial 288 00:21:10.920 --> 00:21:16.799 now in Australia. So we're doing what's called the traditional 289 00:21:17.000 --> 00:21:20.640 sad MAD trial, which is single ascending dose, multiple ascending 290 00:21:20.680 --> 00:21:26.119 dose trial. So we've just completed the single ascending dose 291 00:21:26.200 --> 00:21:32.799 portion of our trial and so healthy volunteers have received 292 00:21:33.359 --> 00:21:36.279 the highest dose of our drug that we intend ever 293 00:21:36.400 --> 00:21:42.920 to give to humans, and it's preliminarily seems to be safe. 294 00:21:43.279 --> 00:21:46.160 And now we've started in the first stage of the 295 00:21:46.279 --> 00:21:51.880 multiple ascending dose. And one innovation that we're doing is 296 00:21:52.799 --> 00:21:56.440 our

phase one trial is being run in Australia, which 297 00:21:56.480 --> 00:22:00.599 isn't particularly innovative. Probably a third of all phrase phase 298 00:22:00.640 --> 00:22:03.839 one trials are being run in Australia these days because 299 00:22:03.880 --> 00:22:06.599 it's a great place to run early stage clinical trials. 300 00:22:07.079 --> 00:22:09.720 But our trial is actually instead of being run by 301 00:22:09.799 --> 00:22:13.920 a private company, it's being run by an academic research organization, 302 00:22:15.039 --> 00:22:19.599 the Victorian Heart Institute, which is headed up by Steve Nichols, 303 00:22:19.680 --> 00:22:28.079 and he has the country's foremost heart hospital and he's 304 00:22:28.119 --> 00:22:31.039 it's just we're super lucky. This is the type of 305 00:22:31.039 --> 00:22:34.640 guy that the big drug companies call to get their 306 00:22:35.400 --> 00:22:38.799 drugs over the final stages, like the help You Little 307 00:22:38.799 --> 00:22:43.400 Aid drugs in phase three. He's worked on those bempaedoic 308 00:22:43.480 --> 00:22:47.440 acid he get those approved. So to have somebody like 309 00:22:47.519 --> 00:22:52.160 him taking an interest in our drug at at such 310 00:22:52.160 --> 00:22:57.279 an early stage is really we're really lucky to have him. 311 00:22:57.839 --> 00:23:01.119 So a little bit more detail about the design of 312 00:23:01.200 --> 00:23:04.720 our trial. We started out at an extraordinarily low dose 313 00:23:04.759 --> 00:23:06.839 of our drug, only one twenty fifth of what we 314 00:23:06.839 --> 00:23:11.200 were eventually intending to dose and scale it up until 315 00:23:11.200 --> 00:23:14.079 we got to where we are now. And we've just 316 00:23:14.119 --> 00:23:17.119 gotten past which is the highest dose, which is twenty 317 00:23:17.119 --> 00:23:23.079 five miligram per kilogram of the recipient. And like I said, 318 00:23:23.119 --> 00:23:27.440 we've started the multiple dose. So of course, the main 319 00:23:27.480 --> 00:23:33.000 outcome that we're looking for is safety, you know, vital signs, reactions, 320 00:23:33.240 --> 00:23:38.960 hearing tests, looking at the pharmacokinetics, how fast the drug 321 00:23:39.039 --> 00:23:43.680 is cleared from from circulation. And then what I'm most 322 00:23:43.720 --> 00:23:46.519 excited about and what the data then I'm really looking 323 00:23:46.559 --> 00:23:49.640 forward to seeing in the coming weeks is the pharmaco 324 00:23:49.720 --> 00:23:52.880 dynamics of the target engagement to see if our drug 325 00:23:53.000 --> 00:23:56.880 is actually grabbing the oxidized cholesterol and pulling it out 326 00:23:57.039 --> 00:24:01.480 of the human patients, out of their blood and into 327 00:24:01.519 --> 00:24:06.440 their urine. So we already have permission. Another nice thing 328 00:24:06.480 --> 00:24:10.680 about doing trials in Australia is that they're quite flexible 329 00:24:10.759 --> 00:24:15.359 with trial design and they've already given us permission once 330 00:24:15.680 --> 00:24:18.079 if our drug has proven to be safe and healthy 331 00:24:18.119 --> 00:24:22.680 young volunteers, we can go straight into a what's called 332 00:24:22.720 --> 00:24:25.920 like a Phase one B type trial in a small 333 00:24:26.000 --> 00:24:30.119 number of human patients who have coronary artery disease. They 334 00:24:30.160 --> 00:24:33.599 have plaque in their cornary artery, and we can dose 335 00:24:33.680 --> 00:24:36.319 them with our drug. We can look for that target engagement, 336 00:24:36.440 --> 00:24:40.000 see if they're peeing out the seven KC. And then 337 00:24:40.519 --> 00:24:44.640 we can look and at blood inflammation markers, which we'd 338 00:24:44.640 --> 00:24:48.200 expect to go down based on some of the data 339 00:24:48.200 --> 00:24:52.920 that I showed you before, and we can do non 340 00:24:52.960 --> 00:25:01.960 invasive imaging of their plaque using CTA aigrams, look at 341 00:25:01.960 --> 00:25:05.480 their plaque before and after treatment and see if if 342 00:25:05.519 --> 00:25:07.799 it improves, see if it gets reduced, see if it 343 00:25:07.799 --> 00:25:12.200 looks less than flamed, that kind of thing. Next is 344 00:25:12.440 --> 00:25:15.599 our phase two plan, which is a scaled up version 345 00:25:15.640 --> 00:25:20.640 of exactly what I just described for late stage phase one, 346 00:25:21.000 --> 00:25:23.319 which will be in about one hundred and fifty patients 347 00:25:24.279 --> 00:25:31.759 who already have a qute cornary arter disease, and we'll 348 00:25:31.799 --> 00:25:34.880 look again at the oxide cholesterol in their blood and 349 00:25:34.920 --> 00:25:37.480 the urine will look at their blood work, see if 350 00:25:37.519 --> 00:25:40.000 it improves, and do the imaging, and then of course 351 00:25:40.039 --> 00:25:45.759 we'll monitor them for heart attacks and strokes, and hopefully 352 00:25:45.759 --> 00:25:49.119 that gets better over the short duration of the phase 353 00:25:49.160 --> 00:25:51.359 two trial. So I want to take a little bit 354 00:25:51.359 --> 00:25:53.559 of a step back before I wrap up and talk. 355 00:25:54.799 --> 00:25:57.519 Just remind you what I said before, which is that 356 00:25:58.119 --> 00:26:01.880 oxided cholesterol plays a role in brain aging because where 357 00:26:01.880 --> 00:26:04.000 do you have the most cholesterol, the highest density of 358 00:26:04.039 --> 00:26:06.440 cluster in your body, It's in your brain. So we're 359 00:26:06.480 --> 00:26:11.279 looking at using our trug for various aspects of aging 360 00:26:11.279 --> 00:26:13.599 in dementia. So we're looking at al Shimer's disease, we're 361 00:26:13.599 --> 00:26:16.799 looking at stroke recovery, and like I said before, we're 362 00:26:16.839 --> 00:26:20.599 interested in macula de generation, and we've recently become interested 363 00:26:20.640 --> 00:26:26.079 in looking at

at liver failure. So we're we've raised 364 00:26:26.519 --> 00:26:29.440 a good amount of money so far to run our 365 00:26:29.480 --> 00:26:33.240 phase one. We're closing on a round of that now 366 00:26:33.319 --> 00:26:36.400 and then we're going to start raising money for our 367 00:26:36.440 --> 00:26:40.960 phase two as so if anybody listening is interested in 368 00:26:40.960 --> 00:26:47.880 investing in Cyclarity Therapeutics, please please reach me. And we're 369 00:26:47.960 --> 00:26:55.359 expecting to make a ideal with a large pharma company 370 00:26:55.519 --> 00:26:59.839 post phase two where we would license out our drug 371 00:27:00.200 --> 00:27:05.279 UDPS year zero three and basically hand it off to 372 00:27:05.359 --> 00:27:08.880 a large pharmaceutical partner to shepherd it through phase three 373 00:27:08.920 --> 00:27:12.119 clinical trials and approval. And marketing and all of that, 374 00:27:13.400 --> 00:27:17.680 and at that point we expect to have a big 375 00:27:17.839 --> 00:27:21.519 return for our investors in three or four years. So 376 00:27:21.599 --> 00:27:25.279 this is the team of amazing people that make this 377 00:27:25.359 --> 00:27:30.039 happen at at psych Clarity here in California. But we've 378 00:27:30.039 --> 00:27:33.920 actually got a team of over one hundred collaborators and 379 00:27:34.880 --> 00:27:40.799 consultants and CROs all around the world and many too 380 00:27:40.799 --> 00:27:47.200 many to thank here. So I'll stop show my disclaimers 381 00:27:47.279 --> 00:27:52.079 and I can stop here and take any questions that 382 00:27:53.119 --> 00:27:53.599 you all have. 383 00:27:54.559 --> 00:27:58.720 Yes, thank you very much Matthew for that very informative presentation, 384 00:27:58.839 --> 00:28:03.519 and we do have some questions from our panel thus far, 385 00:28:03.960 --> 00:28:08.680 So Daniel Tweet wonders, is injection of your drug UDP 386 00:28:09.279 --> 00:28:12.519 zero zero three the only administration route so far? Or 387 00:28:12.559 --> 00:28:14.279 are there other possibilities as well? 388 00:28:14.440 --> 00:28:17.599 There's various aspects of injection that we're looking at. So 389 00:28:18.240 --> 00:28:21.119 all the data that we have so far and all 390 00:28:21.359 --> 00:28:23.359 the work that we've done so far is intervenous. But 391 00:28:23.440 --> 00:28:29.000 we've tested it in animals subcutaneously and it works very well, 392 00:28:29.480 --> 00:28:33.799 and so we're envisioning that it will eventually be released 393 00:28:33.839 --> 00:28:38.839 as either as subcutaneous or intramuscular injection. It could be 394 00:28:40.039 --> 00:28:44.839 like a patch or a pump. It won't. It's unlikely 395 00:28:44.920 --> 00:28:46.519 to be a pill. 396 00:28:49.039 --> 00:28:54.640 Yes, thank you for that answer. And Bill has two questions. 397 00:28:54.920 --> 00:29:00.359 The first question is why CCTA instead of c I 398 00:29:00.519 --> 00:29:02.559 M T. And Bill, I'll let you elaborate on that 399 00:29:02.720 --> 00:29:08.839 question for the laypersons in the audience just a moment. Bill, 400 00:29:08.880 --> 00:29:09.960 you need to unmute. 401 00:29:12.279 --> 00:29:16.599 Why a CTN G Graham instead of a CIMT since 402 00:29:16.640 --> 00:29:19.519 you're looking at the plaque before it's ruptured. 403 00:29:23.119 --> 00:29:28.319 So the CIMT is generally done by ultrasound and CTA 404 00:29:28.440 --> 00:29:30.599 is done by X ray. Just for the audience, I 405 00:29:30.599 --> 00:29:33.839 know you know this, Bill, And you get a better 406 00:29:33.880 --> 00:29:40.759 resolution with CTA and you can look more more deeply 407 00:29:41.519 --> 00:29:47.480 into more hidden blood vessel walls as opposed to being 408 00:29:47.519 --> 00:29:53.039 somewhat restricted to more surface level blood vessels with ultrasound, 409 00:29:53.720 --> 00:29:59.920 so that the most quantitative And this isn't this is 410 00:30:00.079 --> 00:30:04.559 and all coming from me. It's mostly from a cardiologist who 411 00:30:04.920 --> 00:30:08.279 who insists that that CTA is the gold standard right 412 00:30:08.279 --> 00:30:13.279 now in terms of doing really quantitative measurements, uh, you know, 413 00:30:13.319 --> 00:30:19.279 down to the single percent different measurements in plaque thickness 414 00:30:19.599 --> 00:30:23.720 and also being able to see the fat Attenuation Index 415 00:30:24.279 --> 00:30:30.400 UH and which is how dense the plaque is, which 416 00:30:30.519 --> 00:30:33.319 which tells you a lot about the characteristics. So even 417 00:30:33.359 --> 00:30:36.359 if the plaque volume isn't changing, you can tell if 418 00:30:36.400 --> 00:30:39.200 the plaque is getting ready to rupture or if it's 419 00:30:40.000 --> 00:30:42.240 if it's getting less likely to rupture. And you can 420 00:30:42.279 --> 00:30:46.559 also tell things about the inflammation using ai UH layered 421 00:30:46.559 --> 00:30:49.920 on top of the CTA imaging these days, so there's 422 00:30:49.920 --> 00:30:51.559 a lot a lot of data you can get out 423 00:30:51.559 --> 00:30:53.759 of the ct A. The bad thing is that that 424 00:30:53.759 --> 00:30:56.279 that you're exposed to X rays and it's not as 425 00:30:56.319 --> 00:30:58.559 fast and cheap. I wish we were doing both, and 426 00:30:58.759 --> 00:31:01.480 I'd like to move into doing both at some point 427 00:31:01.519 --> 00:31:02.839 in the not too distant future. 428 00:31:03.640 --> 00:31:06.200 Okay, I was misinformed. I guess about c I t 429 00:31:06.319 --> 00:31:08.160 I know you can only do it on the karateid arteries, 430 00:31:08.799 --> 00:31:12.160 but I was thinking that people. 431 00:31:11.960 --> 00:31:16.960 Are less interested. I get into arguments with with the 432 00:31:17.000 --> 00:31:20.119 you know, vascular surgeons and such about this. They I 433 00:31:20.160 --> 00:31:22.240 think the karated is a great

place just as a 434 00:31:22.279 --> 00:31:25.440 marker to look to see if a drug like ours 435 00:31:25.480 --> 00:31:28.000 is working. But they say, oh, why do you want 436 00:31:28.039 --> 00:31:29.640 to look at the crodit It's so easy to do 437 00:31:30.559 --> 00:31:34.039 to do surgery and fix the crowded artery. Uh, so 438 00:31:34.400 --> 00:31:37.799 you know there's no there's no market for for treating 439 00:31:38.839 --> 00:31:42.359 crowded stenosis, just to you know, go after a major 440 00:31:42.440 --> 00:31:47.599 artery like like the cornary artery. And I agree with 441 00:31:47.680 --> 00:31:50.440 you that it's a really nice, easy place to look 442 00:31:50.839 --> 00:31:54.640 for plaque and see it really easily and non invasively. 443 00:31:54.880 --> 00:31:57.279 But I get kind of shouted down by the cardiologists 444 00:31:57.279 --> 00:31:58.559 when I try to make that argument. 445 00:32:00.039 --> 00:32:03.279 Okay, I was actually super impressed, So I take your 446 00:32:03.279 --> 00:32:07.880 word for PCSK nine inhibitors with statins have been shown 447 00:32:07.920 --> 00:32:11.079 to turn salt plaque into hard plaque. It's hard plaque 448 00:32:11.119 --> 00:32:13.640 can to be still filled with oxidized cholesterol. I'm not 449 00:32:13.680 --> 00:32:17.720 sure about that. And will your psyclogextrons get rid of 450 00:32:17.920 --> 00:32:21.000 oxidated cholesterol in hard plack if it is. 451 00:32:21.000 --> 00:32:26.000 Sort yeah, I don't have I have a I have 452 00:32:26.039 --> 00:32:29.839 an answer for you. I don't have a perfectly scientifically 453 00:32:29.839 --> 00:32:32.079 satisfying answer to you. I was really worried about that 454 00:32:32.160 --> 00:32:35.039 when we first developed our drug, about whether or not 455 00:32:35.079 --> 00:32:36.960 it was going to be able to penetrate plaque at all. 456 00:32:37.319 --> 00:32:41.240 And so we got samples of hardened plaque tissue from 457 00:32:41.359 --> 00:32:46.759 patients that it was taken out of surgically, and we 458 00:32:47.400 --> 00:32:51.359 soaked our drug in hardened plaque tissue and it pulled 459 00:32:51.880 --> 00:32:55.240 tons of oxidz cholesterol out of the hardened plau tissue. 460 00:32:55.279 --> 00:32:58.920 I don't know the mechanism by which it penetrates so well. Uh, 461 00:32:59.119 --> 00:33:02.799 there's there's not a good explanation for why our drug 462 00:33:02.880 --> 00:33:07.759 penetrates hardened plaque tissue well. But in our hands, you know, 463 00:33:07.920 --> 00:33:10.799 very preliminarily, it looks like it does, and so I 464 00:33:10.839 --> 00:33:15.720 am optimistic that it will in patients. But it's something 465 00:33:15.759 --> 00:33:18.039 we need to look into more. And I wish there 466 00:33:18.039 --> 00:33:22.039 were better animal models to look at that kind of question. 467 00:33:22.599 --> 00:33:24.759 Again, I was super so the other question I had 468 00:33:24.839 --> 00:33:27.160 was

just combined with the first one. I was super impressed. 469 00:33:27.200 --> 00:33:30.079 I was asking these questions because I've been led to 470 00:33:30.079 --> 00:33:32.599 believe from some clinical studies that I'm trying to get 471 00:33:32.640 --> 00:33:35.279 going that these were the top things to be doing. 472 00:33:35.720 --> 00:33:39.640 But I'm actually thinking what you're doing here might be 473 00:33:39.640 --> 00:33:44.960 better than PCSK nine inhibitors with statins for reducing plaque. 474 00:33:45.799 --> 00:33:46.079 Yeah. 475 00:33:46.160 --> 00:33:49.680 I mean the problem is that those are what's available today, right, 476 00:33:49.839 --> 00:33:55.680 So what's on the market now are LDL lowering drugs. 477 00:33:56.240 --> 00:34:01.279 Statins and PCSK nine inhibitors and the cananighbors might be 478 00:34:01.359 --> 00:34:03.920 working slightly better than status, but they're both doing basically 479 00:34:03.920 --> 00:34:07.599 the same thing, lowering your LDL cholesterol, which has you know, 480 00:34:07.720 --> 00:34:10.559 this bad reputation as being the bad cholesterol, but you 481 00:34:10.599 --> 00:34:14.840 actually need ald L cholesterol. It's how you distribute cholesterol 482 00:34:14.880 --> 00:34:16.880 through your body. Most of the cells in your body 483 00:34:16.920 --> 00:34:19.480 wouldn't have any cholesterol if it wasn't for LDL cholesterol, 484 00:34:19.480 --> 00:34:21.599 so you can't just get rid of it. That's why 485 00:34:21.599 --> 00:34:23.800 I like the oxidized cholesterol as a target, because the 486 00:34:23.800 --> 00:34:26.159 optimal amount of it and your body is zero. If 487 00:34:26.199 --> 00:34:29.320 I could like get rid of It's like lead, right, 488 00:34:29.360 --> 00:34:33.000 what's the optimal amount of lead in your body? It's zero. 489 00:34:33.119 --> 00:34:34.800 So if you could just get rid of all your 490 00:34:34.880 --> 00:34:36.920 lead and all of your oxide cholesterol, you'd just be 491 00:34:37.000 --> 00:34:40.199 better off. And so that's why I like it as 492 00:34:40.400 --> 00:34:43.519 a drug target. And I think it's it's a progression, 493 00:34:43.559 --> 00:34:47.000 it's the next generation. We're going to start seeing the 494 00:34:47.119 --> 00:34:49.159 LP little A drugs coming out I think in the 495 00:34:49.199 --> 00:34:51.440 next year or two, but those are only going to work, 496 00:34:51.440 --> 00:34:54.760 and it's basically a different kind of LDL cholesterol, and 497 00:34:55.000 --> 00:34:58.000 I think to really move the needle towards reversing disease 498 00:34:58.119 --> 00:35:01.119 rather than just slowing it down, which is basically what 499 00:35:01.199 --> 00:35:04.039 the lipid lowering drugs do, We're going to need something 500 00:35:04.599 --> 00:35:08.239 more aggressive that can reverse disease. 501 00:35:08.639 --> 00:35:10.800 So did you just say you're targeting you have something 502 00:35:10.800 --> 00:35:12.400

that's going to be targeting LP little A. 503 00:35:13.400 --> 00:35:16.440 No, no, No, I was just saying the next big 504 00:35:16.519 --> 00:35:18.920 heart disease drugs that are going to be released. I'm 505 00:35:18.960 --> 00:35:23.480 predicting because there's several big drug companies that have them 506 00:35:23.480 --> 00:35:27.639 in late stage phase three clinical trials and they seem 507 00:35:27.639 --> 00:35:30.960 to be working reasonably well. Are going to be LP 508 00:35:31.079 --> 00:35:35.480 little A lowering drugs, and we will be the next 509 00:35:35.519 --> 00:35:37.920 generation of drugs after those, I believe. 510 00:35:39.920 --> 00:35:45.079 Yes, very interesting. So that gives rise to a hypothetical 511 00:35:45.159 --> 00:35:51.400 question for me. So, if cholesterol exists in the bloodstream 512 00:35:51.480 --> 00:35:54.800 but it doesn't get oxidized, if you take care of 513 00:35:54.840 --> 00:35:59.400 all of the oxidized cholesterol, does the non oxidized cholesterol 514 00:35:59.480 --> 00:36:03.760 pose any risk of atherosclerosis or can the macrophages that 515 00:36:03.840 --> 00:36:08.639 you mentioned digest any other cholesterol to render it harmless. 516 00:36:10.159 --> 00:36:11.760 Yeah, I mean that's a big part of the job 517 00:36:11.800 --> 00:36:15.719 of the macrophage is is to collect the cholesterol and 518 00:36:16.039 --> 00:36:19.760 recycle it send it back to your liver. So that's 519 00:36:19.840 --> 00:36:24.880 what that's what should happen. The issue is that you 520 00:36:25.000 --> 00:36:30.360 always have oxygen free radicals around, so it's just it's 521 00:36:30.400 --> 00:36:33.440 like rusting. It literally is rusting, right, it's the rusting 522 00:36:33.480 --> 00:36:37.519 process of oxygen reacting in this case with cholesterol instead 523 00:36:37.519 --> 00:36:39.480 of like metal on your car or something like that. 524 00:36:39.599 --> 00:36:39.760 Right. 525 00:36:40.599 --> 00:36:44.639 But it's a similar process, and so it's going to 526 00:36:44.719 --> 00:36:49.599 keep happening. And so if you have elevated cholesterol, it's 527 00:36:49.960 --> 00:36:52.679 and you have the same amount of oxidation. If you 528 00:36:52.719 --> 00:36:55.800 increase either oxidation or cholesterol, you're going to end up 529 00:36:55.800 --> 00:37:02.360 with more oxidized cholesterol. So people with elevated cholesterol tend 530 00:37:02.559 --> 00:37:05.880 to have more oxidized cholesterol in their system. It's not 531 00:37:05.920 --> 00:37:08.559 a one to one because you can have more oxidation 532 00:37:08.639 --> 00:37:11.239 in your system for various reasons. And we don't exactly 533 00:37:11.320 --> 00:37:14.519 understand why there are people walking around with like normal 534 00:37:14.599 --> 00:37:17.800 levels of cholesterol but really high levels of oxidized cholesterol. 535 00:37:18.280 --> 00:37:22.360 And is it possible to have the opposite scenario where 536 00:37:22.360 --> 00:37:26.760 someone has high levels of cholesterol overall but low levels 537 00:37:26.760 --> 00:37:29.880 of oxidized cholesterol for whatever reason, or do we not 538 00:37:30.039 --> 00:37:33.519 observe that unless that person has been treated with something 539 00:37:33.719 --> 00:37:35.960 like UDP zero zero three. 540 00:37:36.199 --> 00:37:38.920 You know, there are people who do seem to be 541 00:37:39.039 --> 00:37:43.760 somewhat resistant to walking around with high cholesterol. I don't 542 00:37:43.760 --> 00:37:47.079 think it's well studied enough to say that they aren't 543 00:37:47.119 --> 00:37:52.960 accumulating oxidized cholesterol in various places in their bodies, whether 544 00:37:53.039 --> 00:37:55.960 or not they develop atheroschrosis at a young age like 545 00:37:56.719 --> 00:38:01.199 most of them do. I think they're probably building up 546 00:38:01.199 --> 00:38:06.039 oxized cholesterol someplace where we're not looking, like in the brain, 547 00:38:06.119 --> 00:38:09.519 which is really hard to buyopsy. You can only look 548 00:38:09.559 --> 00:38:13.440 at it pretty much after somebody dies, and other tissues 549 00:38:13.480 --> 00:38:13.920 as well. 550 00:38:15.559 --> 00:38:18.599 Yes, thank you for that answer. And Bill has a question. 551 00:38:19.119 --> 00:38:24.199 Do antioxidants reduce the levels of oxidized cholesterol or can 552 00:38:24.360 --> 00:38:25.960 some antioxidants do that? 553 00:38:28.320 --> 00:38:32.599 You know, I it's something that some groups have looked 554 00:38:32.639 --> 00:38:36.119 into a little bit. It, I mean mostly antioxidants have 555 00:38:36.280 --> 00:38:40.719 been kind of a disappointment in general in medicine and 556 00:38:40.760 --> 00:38:41.760 anti aging medicine. 557 00:38:41.800 --> 00:38:41.960 Right. 558 00:38:41.960 --> 00:38:45.119 They haven't proven to be very effective. Now, the counter 559 00:38:45.199 --> 00:38:48.079 argument to that is that we haven't built good enough 560 00:38:48.440 --> 00:38:52.079 antioxidants yet. We haven't targeted them for the right places 561 00:38:52.360 --> 00:38:56.599 or something like that. So I think there's potential room 562 00:38:56.639 --> 00:39:02.599 for that. But you can't reduce your oxygen free radicals 563 00:39:02.639 --> 00:39:08.480 to zero. You can't like completely prevent all oxygen free 564 00:39:08.519 --> 00:39:12.039 radicals from forming, no matter how many antioxidants you take. 565 00:39:12.280 --> 00:39:15.960 So that's why I follow this kind of damage repair 566 00:39:16.079 --> 00:39:25.280 philosophy philosophy approach. You know, Generally, my approach to studying 567 00:39:25.519 --> 00:39:29.599 and trying to remediate the aging process and and therapeutically 568 00:39:30.079 --> 00:39:31.960 is that I think it's the best place to intervene. 569 00:39:32.039 --> 00:39:36.599 But there is potential to see I haven't seen yet 570 00:39:36.639 --> 00:39:41.599 a

convincing study showing that that there's good antioxidant evidence 571 00:39:41.679 --> 00:39:46.159 showing reduction in oxidized cholesterol levels in a person, but 572 00:39:46.519 --> 00:39:48.480 I don't think it's been studied enough, and I think 573 00:39:48.960 --> 00:39:53.039 better studies with better antioxidants could work to some extent 574 00:39:53.079 --> 00:39:58.920 with it. And perhaps we've started a small project looking 575 00:39:59.000 --> 00:40:02.559 at some kind of combin therapy in that realm, in 576 00:40:02.960 --> 00:40:06.440 a model system that we're looking at that maybe it 577 00:40:06.480 --> 00:40:10.119 could be helpful, especially since you get when you have 578 00:40:10.239 --> 00:40:13.599 high inflammation in someplace like a plaque, you also get 579 00:40:13.679 --> 00:40:18.960 high levels of oxidation and so if you combine, if 580 00:40:19.000 --> 00:40:23.760 you combine antioxidation with getting rid of oxidized cholesterol, maybe 581 00:40:23.760 --> 00:40:25.119 we'll get a synergistic effect. 582 00:40:26.159 --> 00:40:28.920 Very interesting, Thank you very much. And we have a 583 00:40:29.000 --> 00:40:32.400 number of questions from Daniel Tweed as well. Let's start 584 00:40:32.440 --> 00:40:37.360 with the questions that focus on the name of the drug, 585 00:40:37.559 --> 00:40:41.639 and Daniel is curious about the origins of the name 586 00:40:41.719 --> 00:40:44.360 u DP zero zero three. Is that a chemical name 587 00:40:44.400 --> 00:40:45.639 shorthand of some sort. 588 00:40:46.880 --> 00:40:51.880 It's so UDP stands for Underdog Pharmaceuticals, which was the 589 00:40:51.920 --> 00:40:57.039 original name of our company, and then we changed our 590 00:40:57.119 --> 00:41:00.039 company named as Cyclarity Therapeutics a few years ago. So 591 00:41:00.920 --> 00:41:06.079 we just we did the kind of boring but efficient thing, 592 00:41:06.159 --> 00:41:12.719 which was numbering our compounds from starting from one as 593 00:41:12.760 --> 00:41:17.039 we invented them. And yeah, it'll get a more exciting 594 00:41:17.119 --> 00:41:20.280 name at some point. I didn't want to give it 595 00:41:20.480 --> 00:41:25.840 a sexy name too early, because what I see happening 596 00:41:25.960 --> 00:41:28.239 is that you get your favorite name and you name it, 597 00:41:28.280 --> 00:41:30.840 and then you get a partnership or you get a 598 00:41:30.840 --> 00:41:33.159 new big investor and they don't like your name and 599 00:41:33.159 --> 00:41:35.119 they make you change the name. And then you see 600 00:41:35.199 --> 00:41:38.519 drugs go through like three, four or five different names 601 00:41:38.559 --> 00:41:42.079 before they actually get you know, widespread on the market, 602 00:41:42.119 --> 00:41:45.000 and I figured out just wait a little while before we, 603 00:41:45.320 --> 00:41:48.519 you know, get get married to a name. But if 604 00:41:48.519 --> 00:41:52.760 people have ideas for names for us, send them to me, 605 00:41:52.840 --> 00:41:55.719 and we're starting to make a list. 606 00:41:56.719 --> 00:42:02.239 Yes, So for those viewers watching this virtual Enlightenment salon, 607 00:42:02.360 --> 00:42:06.119 please put any ideas you have for a name for 608 00:42:06.679 --> 00:42:10.840 UDP zero zero three that might eventually be used in 609 00:42:11.360 --> 00:42:16.239 our YouTube chat and we will relay them to OK 610 00:42:17.039 --> 00:42:21.159 And in the meantime, Daniel has another question. He notes 611 00:42:21.519 --> 00:42:26.079 this scavenging therapy molecule sounds like it has benefits for 612 00:42:26.360 --> 00:42:30.119 both new as well as long term users, and he 613 00:42:30.199 --> 00:42:33.719 wants to know if that's correct given that this process 614 00:42:33.840 --> 00:42:39.039 of oxidation happens continuously. So would you expect that this 615 00:42:39.119 --> 00:42:42.679 is a drug that could also be administered over the 616 00:42:42.760 --> 00:42:48.280 long term for someone to prevent the formation of atherosclerotic plas. 617 00:42:48.920 --> 00:42:49.159 Yeah. 618 00:42:49.199 --> 00:42:51.920 I think it can be a preventative as well as 619 00:42:52.360 --> 00:42:56.039 a reversal agent. And I hope we see a day 620 00:42:56.280 --> 00:43:01.199 when based on a biomarker task like sized cholesterol in 621 00:43:01.239 --> 00:43:05.360 your blood or in a tissue sample, you can take 622 00:43:05.880 --> 00:43:08.400 our drug and that you don't have to wait until 623 00:43:08.440 --> 00:43:10.960 you're one of your blood vessels is like more than 624 00:43:10.960 --> 00:43:14.000 fifty percent included when you start having trouble you know, 625 00:43:14.039 --> 00:43:16.840 climbing stairs or breathing or getting chest pain or something 626 00:43:16.880 --> 00:43:19.400 like that, or having a know hour attack before you 627 00:43:19.440 --> 00:43:25.360 ever get diagnosed with having atheroscrosis. So yeah, so I 628 00:43:25.360 --> 00:43:28.280 think it can be preventive as well as a reversal. 629 00:43:28.559 --> 00:43:31.880 I don't think that you will need to take it continuously, 630 00:43:32.039 --> 00:43:34.559 like every day or something like that. I think you 631 00:43:34.599 --> 00:43:39.400 can take it intermittently and we hope that you will 632 00:43:39.480 --> 00:43:43.639 just have to take approximately six doses in a row 633 00:43:44.360 --> 00:43:48.000 over a couple of weeks. Our current protocol is over 634 00:43:48.039 --> 00:43:51.639 the course of sixteen days, every third day you get 635 00:43:51.679 --> 00:43:54.079 a dose and that that should get rid of the 636 00:43:54.199 --> 00:43:57.639 vast majority of the oxidzed cholesterol in your system. And 637 00:43:57.679 --> 00:44:00.719 that's taken decades for it to build up. Hopefully you 638 00:44:00.760 --> 00:44:02.400 don't have to come back for another five or ten 639 00:44:02.480 --> 00:44:05.960

years for another course of treatment. So maybe people are 640 00:44:05.960 --> 00:44:11.719 going to start getting this when they're symptomatic in their sixties, say, 641 00:44:12.719 --> 00:44:16.880 but later on, maybe we'll be taking it in you know, 642 00:44:17.000 --> 00:44:20.079 our thirties or forties, every you know, five or ten 643 00:44:20.159 --> 00:44:22.960 years to make sure you don't get sick from that stuff. 644 00:44:23.559 --> 00:44:26.880 Yes, indeed, and would you pair that with some sort 645 00:44:26.960 --> 00:44:32.800 of diagnostic tests, say a blood test to measure the 646 00:44:33.239 --> 00:44:37.719 oxidized cholesterol, the seven keto cholesterol, rather than just the 647 00:44:37.760 --> 00:44:39.840 total cholesterol or the LDL. 648 00:44:40.360 --> 00:44:46.639 Eventually, we're not developing a there's not a commercially available 649 00:44:47.159 --> 00:44:50.559 seven k C. There's two kinds of blood tests you 650 00:44:50.559 --> 00:44:54.760 can do for oxidized cholesterol. One is for oxidized LDL, 651 00:44:55.000 --> 00:44:57.400 which there is a test for and you can you 652 00:44:57.440 --> 00:45:00.880 can go and get Our drug should not not directly 653 00:45:01.599 --> 00:45:07.079 remove ox LDL. Our drug isn't meant to attack LDL 654 00:45:07.239 --> 00:45:11.360 or HDL. It's meant to attack cells and tissues. So 655 00:45:11.480 --> 00:45:14.920 what ox LDL does is it delivers seven k C 656 00:45:15.440 --> 00:45:18.880 to the blood vessel walls and two macrophases, and so 657 00:45:19.000 --> 00:45:22.000 then our drug can go into the macrophages and pull 658 00:45:22.000 --> 00:45:24.599 it out after it's been delivered. So you can get 659 00:45:24.639 --> 00:45:27.360 a test for ox LDL, but our drug shouldn't be 660 00:45:27.719 --> 00:45:32.000 lowering ox l dl. We can test in our clinical trial. 661 00:45:32.000 --> 00:45:36.800 We are testing people for blood and you're in oxidized 662 00:45:36.840 --> 00:45:43.119 cholesterol seven keto cholesterol. But we're not developing a diagnostic 663 00:45:43.679 --> 00:45:47.440 that we're intending to know to release and sell to 664 00:45:47.519 --> 00:45:51.360 the public. I think that the world will be better 665 00:45:51.400 --> 00:45:54.639 off if and when there is such an approved diagnostic. 666 00:45:54.639 --> 00:45:57.280 We're doing a little bit of work trying to invent 667 00:45:57.440 --> 00:46:03.239 a faster, cheaper method of measuring seven keto cholesterol so 668 00:46:03.320 --> 00:46:07.440 that US or somebody else, a diagnostics company could could 669 00:46:07.480 --> 00:46:09.920 take that and turn it into a diagnostic test that 670 00:46:09.960 --> 00:46:14.920 patients could take. To your question about what it will 671 00:46:14.960 --> 00:46:17.239 be paired with when it's first released, it will probably 672 00:46:17.280 --> 00:46:20.800 be paired with with with andiogram. So you'll get a 673 00:46:20.840 --> 00:46:25.000 scan

of your of your say, coronary artery, and it'll 674 00:46:25.039 --> 00:46:27.679 be blocked, and you'll take our drug and you'll come 675 00:46:27.719 --> 00:46:30.519 back in six months or a year and get another 676 00:46:30.599 --> 00:46:34.679 scan and hopefully it will have improved, and maybe it'll 677 00:46:34.679 --> 00:46:36.760 have improved, but it won't have improved as much as 678 00:46:36.760 --> 00:46:38.920 your cardiologist wants, and so they'll give you another course 679 00:46:38.920 --> 00:46:39.440 of treatment. 680 00:46:39.920 --> 00:46:40.039 Uh. 681 00:46:40.199 --> 00:46:42.800 And they could do that, you know, once every year 682 00:46:42.880 --> 00:46:46.639 or so until they're satisfied that you're better. But I 683 00:46:46.760 --> 00:46:49.519 eventually I hope that it gets reduced to an easier 684 00:46:49.559 --> 00:46:55.400 biomarker like a blood test. Yes, thank you. 685 00:46:55.599 --> 00:47:00.480 And that leads into the question from Daniel tweet. How 686 00:47:00.679 --> 00:47:03.960 affordable would this therapy be in vision to. 687 00:47:03.960 --> 00:47:13.079 Be well, we expected to be covered by insurance. We're 688 00:47:13.119 --> 00:47:20.800 planning to two uh to to release it you know 689 00:47:20.840 --> 00:47:25.800 widely in uh in all the you know markets around 690 00:47:25.840 --> 00:47:26.159 the world. 691 00:47:26.760 --> 00:47:26.880 Uh. 692 00:47:27.719 --> 00:47:31.960 It's not going to be you know, uh a dollar 693 00:47:32.079 --> 00:47:34.840 or ten dollars a treatment. It's probably going to be 694 00:47:36.119 --> 00:47:39.719 at least a few thousand dollars for a treatment. And 695 00:47:39.800 --> 00:47:43.079 that we don't know the market economics get it's probably 696 00:47:43.079 --> 00:47:45.639 going to be thousands of dollars for a treatment. 697 00:47:46.280 --> 00:47:46.400 Uh. 698 00:47:47.639 --> 00:47:51.800 And but you know, I think that's it's more expensive 699 00:47:51.920 --> 00:47:55.280 than like a statin, but it's going to be cheaper 700 00:47:55.320 --> 00:48:01.199 than a gene therapy or and competitive with the therapeutic antibiodies. 701 00:48:02.440 --> 00:48:05.360 Yes, and as you said, hopefully the few thousand dollars 702 00:48:05.400 --> 00:48:11.920 per treatment will be administered every fairly large number of years, 703 00:48:11.960 --> 00:48:15.639 like five or ten years, rather than say, every year. 704 00:48:15.920 --> 00:48:19.639 So thank you for that answer. And Bill also wonders 705 00:48:19.679 --> 00:48:23.800 with regard to the comment about the angiogram, will you 706 00:48:23.920 --> 00:48:28.480 DP zero zero three reduce clocks also or at least 707 00:48:28.480 --> 00:48:29.840 have that tendency to do that. 708 00:48:30.800 --> 00:48:33.920 Let me say I was miss I was thinking differently 709 00:48:33.920 --> 00:48:36.800 when I asked that question. I was forgetting that regular 710 00:48:36.840 --> 00:48:42.599 angigrams can detect large plaque bulges too, so, but but yeah, 711 00:48:42.840 --> 00:48:45.320 is there any chance that this would help with ruptured 712 00:48:45.360 --> 00:48:47.280 plaques When a clock gets formed. 713 00:48:47.800 --> 00:48:51.960 Our drug acts quickly in terms of removing oxide cholesterol, 714 00:48:51.960 --> 00:48:56.280 but it acts slowly in terms of allowing the macrophage 715 00:48:56.480 --> 00:48:59.320 then to go back to doing its job and cleaning 716 00:48:59.400 --> 00:49:02.280 up the plaque. So our drug isn't designed to work 717 00:49:02.360 --> 00:49:07.880 like draino and flush out your arteries in in minutes. 718 00:49:08.880 --> 00:49:12.199 It's meant to flush out all your oxidized cholesterol and 719 00:49:12.239 --> 00:49:15.119 then for it to heal over the course of weeks 720 00:49:15.119 --> 00:49:19.239 and months. So you wouldn't want to rely on our 721 00:49:19.360 --> 00:49:23.239 drug if you were like in an ambulance needing like 722 00:49:23.280 --> 00:49:28.440 a cloudbuster, you know, because you're the you know, the 723 00:49:28.440 --> 00:49:33.440 blood flow to your brain has been been blocked. That said, 724 00:49:33.719 --> 00:49:39.679 there's clouding, there's clotting that happens inside of plaque, and 725 00:49:39.679 --> 00:49:43.880 and ruptured plaque can get stuck places where it's not 726 00:49:44.239 --> 00:49:49.480 very easy to remove surgically, and you know, sometimes there's 727 00:49:49.519 --> 00:49:52.760 decisions about whether to leave it alone or monitor it, 728 00:49:52.880 --> 00:49:56.159 or go in and remove it. And so in some 729 00:49:56.239 --> 00:50:01.280 of those edge cases where it's where a wait and 730 00:50:01.320 --> 00:50:06.119 see uh approach might work better than maybe our drug 731 00:50:06.119 --> 00:50:08.880 with help. But I'm just sort of I'm kind of 732 00:50:08.960 --> 00:50:10.679 rambling because I'm thinking about this on the flat, because 733 00:50:10.679 --> 00:50:12.360 I haven't thought about that question before. 734 00:50:12.400 --> 00:50:16.079 About There's another question I had, and that's because I 735 00:50:16.119 --> 00:50:18.679 was doing some Google searches while you were answering some 736 00:50:18.719 --> 00:50:23.639 other questions. But on cyclodextrons, I saw that there's two 737 00:50:23.719 --> 00:50:30.480 hydroxy propyle beta cyclodextrin that's already available for getting rid 738 00:50:30.480 --> 00:50:34.440 of oxidized cholesterol. Is that is yours comparable to that? 739 00:50:34.519 --> 00:50:36.360 And it didn't look like that's used as a dimer 740 00:50:36.440 --> 00:50:37.000 like yours is. 741 00:50:38.599 --> 00:50:43.039 Yeah, so what you're Yeah, well, you're the two hydroxypropyle 742 00:50:43.079 --> 00:50:46.599 beta cyclodextrin or just hydroxyprople beta cyclod extrin or h 743 00:50:46.679 --> 00:50:53.079 pbc D. It's been around for decades. It's it's used 744 00:50:53.119 --> 00:50:55.639 in in foods, it's

used in I think it's in 745 00:50:55.679 --> 00:51:00.639 for breeze. It's it's it's used to deliver drugs. It's 746 00:51:00.719 --> 00:51:03.320 it's very safe, you can inject it at very high doses, 747 00:51:03.800 --> 00:51:06.960 you can eat it. There's there's food grid hydroxy public 748 00:51:07.000 --> 00:51:11.360 beta cyclodextra and so should you get injected with it 749 00:51:12.320 --> 00:51:16.360 in order to get treated safe for you know, aging 750 00:51:16.480 --> 00:51:20.079 or atheroschrosis something like that, or or other diseases. There 751 00:51:20.079 --> 00:51:24.000 are actually two companies that are trying to use that 752 00:51:24.719 --> 00:51:28.039 substance to treat Niemann Pick type CE disease, which is 753 00:51:29.000 --> 00:51:33.119 a rare licens almost storage disorder, which is a cholesterol 754 00:51:33.159 --> 00:51:38.719 transporter disorder. Now, hydroxy probably beta cyclodextrin doesn't bind cholesterol 755 00:51:39.199 --> 00:51:41.840 very well at all. It's a very very weak, if 756 00:51:41.880 --> 00:51:45.079 at all, binder of cholesterol. But they figure this stuff 757 00:51:45.119 --> 00:51:47.760 is so safe and it's approved for like anything that 758 00:51:47.800 --> 00:51:51.280 you want to use it for. Uh, So we're going 759 00:51:51.360 --> 00:51:54.679 to take these kids and dose them with like enormous 760 00:51:54.760 --> 00:51:57.079 enormous quantities of this stuff and see if it helps. 761 00:51:57.519 --> 00:51:59.559 Because it did help in animal model. So if you 762 00:51:59.599 --> 00:52:05.079 give an animal with this name and Pick disease, this 763 00:52:06.159 --> 00:52:10.199 hydroxy prople beta cyclduxtrain when they're very young, it helps. 764 00:52:10.480 --> 00:52:13.000 It does help a lot. I suspect it is helping 765 00:52:13.079 --> 00:52:16.760 the patients. It's been a little difficult for these companies 766 00:52:16.800 --> 00:52:19.079 to prove that it's helping because these patients are so 767 00:52:19.280 --> 00:52:23.679 sick and have so much brain damage that it's hard 768 00:52:23.679 --> 00:52:27.760 to tell if they're getting better. I think they're living 769 00:52:27.800 --> 00:52:30.880 longer with a very poor standard of living. I think 770 00:52:30.920 --> 00:52:35.000 the drug is very weak but probably effective at extraordinarily 771 00:52:35.079 --> 00:52:37.960 high doses. And the kind of doses that you need 772 00:52:38.039 --> 00:52:41.440 to make it effective since it's such an inactive compound, 773 00:52:42.000 --> 00:52:44.320 is like having one of these kids trying to lie 774 00:52:44.360 --> 00:52:47.679 still on a table getting a IB for like six 775 00:52:47.719 --> 00:52:51.000 hours or something like that. So I think our drug 776 00:52:51.000 --> 00:52:53.440 would work better for name and Pick disease. We're not 777 00:52:53.719 --> 00:52:56.480 working on that, but I'd love to be working on 778 00:52:56.519 --> 00:53:00.199 that someday. And I think it would be this same 779 00:53:00.320 --> 00:53:04.239 kind of thing if HPbCD could help you with others races, 780 00:53:04.320 --> 00:53:06.440 I think you would need to be getting an IV 781 00:53:06.719 --> 00:53:10.000 bag full of it frequently in order for it to 782 00:53:10.000 --> 00:53:14.079 have an effect. It's just not a drug. It's you know, 783 00:53:14.199 --> 00:53:17.199 it's it's something that is a very weak binder of 784 00:53:17.239 --> 00:53:19.760 a lot of things. So I don't know what else 785 00:53:19.800 --> 00:53:22.199 it's binding when it's going in there, But you know, 786 00:53:22.280 --> 00:53:27.079 it's pretty safe stuff, so it probably doesn't hurt. But 787 00:53:27.440 --> 00:53:31.239 I mean it's been shown to cause hearing loss at 788 00:53:31.400 --> 00:53:33.639 very high doses in rodents, so that's something that some 789 00:53:33.679 --> 00:53:37.039 people are concerned about. You just need to stay clear 790 00:53:37.079 --> 00:53:40.800 of those hearing loss toxic doses. 791 00:53:41.119 --> 00:53:44.719 Interesting. Thank you very much, and we've got a few 792 00:53:44.800 --> 00:53:49.639 questions from Daniel. He wonders could this be used to 793 00:53:49.679 --> 00:53:54.000 externally process a patient's blood in a kind of dialysis 794 00:53:54.079 --> 00:53:57.079 modality or would that not make sense? I think Daniel, 795 00:53:57.119 --> 00:54:02.519 what you're considering is perhaps taking a patient's blood and 796 00:54:02.599 --> 00:54:06.519 applying the drug to it outside of the patient's body 797 00:54:06.559 --> 00:54:10.159 and then doing some sort of like therapeutic plasma exchange 798 00:54:10.199 --> 00:54:13.440 where you pump in the clean blood and replace the 799 00:54:13.519 --> 00:54:17.039 existing blood with it. Or would that not really take 800 00:54:17.079 --> 00:54:21.920 care of the problem, which would be that cholesterol accumulating 801 00:54:21.960 --> 00:54:22.719 in the arteries. 802 00:54:23.119 --> 00:54:26.079 Yeah, it's a good question, and it's something we thought 803 00:54:26.119 --> 00:54:31.039 about for a while. So one problem with the approach 804 00:54:31.280 --> 00:54:35.280 is the last thing that you just said, Jenity, which 805 00:54:35.320 --> 00:54:39.119 is that you could pull all of the oxide. Using 806 00:54:39.159 --> 00:54:40.719 a method like that, you could pull all the oxides 807 00:54:40.760 --> 00:54:43.079 cholesterol out of the blood stream, but you couldn't. You 808 00:54:43.079 --> 00:54:46.400 wouldn't be delivering your drug to the system and letting 809 00:54:46.440 --> 00:54:50.920 our drug go into your blood vessel walls and any 810 00:54:50.960 --> 00:54:54.360 other tissues where it might be able to pull oxide 811 00:54:54.440 --> 00:54:59.000 cholesterol out of now, that doesn't mean we haven't thought 812 00:54:59.039 --> 00:55:00.440 about it and that it might not be a good 813 00:55:00.480 --> 00:55:02.760

therapeutic approach. What we haven't been able to think of 814 00:55:02.800 --> 00:55:06.239 a way to do is, so you know, you take 815 00:55:06.320 --> 00:55:08.559 the drug, you take the blood out of the body, 816 00:55:08.599 --> 00:55:13.679 and then you put our drug in there. Presumably you 817 00:55:13.719 --> 00:55:16.320 want to pull the drug out before putting it back 818 00:55:16.400 --> 00:55:18.519 into the body or else like why did you go 819 00:55:18.599 --> 00:55:21.519 through this process rather than just delivering it into the body. 820 00:55:21.760 --> 00:55:23.840 So we haven't been able to think of a way 821 00:55:24.000 --> 00:55:29.239 to clear our drug out of the blood stream as 822 00:55:29.239 --> 00:55:30.519 a part of that process. 823 00:55:30.679 --> 00:55:30.960 Yet. 824 00:55:31.559 --> 00:55:34.519 If there's people listening who are interested in the in 825 00:55:34.920 --> 00:55:37.280 how that might work, or think they might understand something 826 00:55:37.320 --> 00:55:40.679 about the how to make that work in a kind 827 00:55:40.719 --> 00:55:43.199 of like a sort of a dialysis sort of approach, 828 00:55:43.480 --> 00:55:45.840 we're interested in that as approach, but we haven't started 829 00:55:45.840 --> 00:55:50.039 playing with it yet, but it's it's a cool idea 830 00:55:50.039 --> 00:55:51.320 that we want to work on sometime. 831 00:55:52.599 --> 00:55:56.639 Yes, thank you very much for that answer. And Daniel's 832 00:55:56.639 --> 00:56:00.719 other question is could targeted cyclodextrins be created did using 833 00:56:01.079 --> 00:56:05.800 a suitably genetically engineered cell, such as perhaps an E. 834 00:56:05.880 --> 00:56:09.679 Coli bacterium that could be harnessed for that purpose, like, 835 00:56:09.760 --> 00:56:14.039 could you reconfigure one of those to produce the cyclodextrons. 836 00:56:14.360 --> 00:56:18.880 So the core building blocks are built by by microbes, 837 00:56:19.000 --> 00:56:25.840 but I've never heard of a microbe building a modified cyclodextrin. 838 00:56:26.119 --> 00:56:28.480 Like the example that Bill was asking me about earlier 839 00:56:28.599 --> 00:56:32.119 is a hydroxy propylated cyclodextrin. So you take a hydroxypropyle 840 00:56:32.199 --> 00:56:36.320 chemical group and stick it onto a onto a cyclodextrin. 841 00:56:36.320 --> 00:56:38.599 Which is part of the power of cyclodextrins is how 842 00:56:39.159 --> 00:56:43.519 you could there's potentially hundreds or you know, theoretically infinite 843 00:56:44.119 --> 00:56:46.719 different types of chemical groups that you could stick onto 844 00:56:46.719 --> 00:56:49.880 a cyclodextrin and then a cyclodextrian. There's three different sizes 845 00:56:49.920 --> 00:56:53.280 of cyclodextrians. The cyclodextrins that we're using are the medium size, 846 00:56:53.760 --> 00:56:57.239 and we're making dimers of them. Our dimers have forty 847 00:57:00.639 --> 00:57:05.480 sites on them where you

could potentially put any of 848 00:57:05.519 --> 00:57:08.480 these chemical groups that you want, so they're kind of 849 00:57:08.599 --> 00:57:14.639 infinitely engineerable. Now I've never heard of a microbe figuring 850 00:57:14.679 --> 00:57:18.639 out how to do that chemistry on its own, but 851 00:57:18.679 --> 00:57:21.280 they're very good at producing the core building blocks, and 852 00:57:21.320 --> 00:57:24.360 that's how they're how the building blocks are made that 853 00:57:24.400 --> 00:57:28.719 we buy and then use to do our synthetic chemistry 854 00:57:28.760 --> 00:57:31.920 on top of that, But I've never heard of somebody 855 00:57:31.960 --> 00:57:34.800 figuring out how to how to culture, how to like 856 00:57:34.920 --> 00:57:40.320 grow substituted We call them substituted cyclodextrons like in a vat. 857 00:57:41.880 --> 00:57:47.719 Yes, thank you for that answer. And Daniel wonders, a 858 00:57:47.800 --> 00:57:51.440 dimer is a chemical pairing of identical molecules. Yes, that's 859 00:57:51.519 --> 00:57:56.920 the definition. Essentially, a molecule or molecular complex consisting of 860 00:57:56.920 --> 00:58:00.760 two identical molecules or subunits that are link together. 861 00:58:01.559 --> 00:58:04.639 But you don't necessarily, so you could have the dimer, 862 00:58:04.679 --> 00:58:06.760 and you could imagine that on one side of the 863 00:58:06.800 --> 00:58:11.280 dimer you have one kind of chemistry and on the 864 00:58:11.320 --> 00:58:13.320 other dimer you have another kind of chemistry. And we 865 00:58:13.360 --> 00:58:17.199 can do that kind of chemistry. Uh, when we engineer 866 00:58:17.360 --> 00:58:21.400 our dimers, and that is part of our intellectual property 867 00:58:21.960 --> 00:58:26.079 is making the two different halves different, so that if 868 00:58:26.079 --> 00:58:31.199 you have an asymmetrical target, you could engineer one side 869 00:58:31.599 --> 00:58:36.159 to grab one side of your target in a certain 870 00:58:36.199 --> 00:58:39.360 way and the other side so you could work on 871 00:58:39.719 --> 00:58:41.559 you know, the charge, So if you're looking at a 872 00:58:41.679 --> 00:58:44.800 charged target, you could put the opposite charge on one 873 00:58:44.840 --> 00:58:47.519 side of the cycled extrin and not on the other side. 874 00:58:48.159 --> 00:58:51.039 If if once, if your target is like has like 875 00:58:51.079 --> 00:58:54.199 a skinny and a fat side like that, you could 876 00:58:54.239 --> 00:58:57.119 make your your cycled extra more more narrow on one 877 00:58:57.159 --> 00:58:59.360 side and fatter on the other. Those are all things 878 00:58:59.360 --> 00:59:01.679 that we play with a lot when we're in the 879 00:59:01.760 --> 00:59:05.159 early stages of engineering our cyclic extrons at the computational 880 00:59:05.199 --> 00:59:07.679 and then synthetic level very interesting. 881 00:59:07.719 --> 00:59:11.920 So the dimers are more versatile

than they may appear 882 00:59:12.000 --> 00:59:15.719 at first glance, at least with your approach. Now, one 883 00:59:16.119 --> 00:59:20.119 question that I'm curious about is in regard to your 884 00:59:20.159 --> 00:59:23.280 future plans. In the event that the phase two trials 885 00:59:23.320 --> 00:59:26.039 are successful, you stated you would make a deal with 886 00:59:26.079 --> 00:59:30.679 a large pharma company to essentially manufacture and sell this drug. 887 00:59:31.280 --> 00:59:35.920 Would you plan for a deal where Cyclarity would maintain 888 00:59:36.000 --> 00:59:38.920 the intellectual property and then the pharma company would pay 889 00:59:38.960 --> 00:59:41.320 you royalties over time to use it. Or would you 890 00:59:41.440 --> 00:59:45.280 just sell the intellectual property in one lump sum and 891 00:59:45.440 --> 00:59:49.400 let the pharma company do what it pleases thereafter. 892 00:59:50.039 --> 00:59:53.559 There's a lot of potential ways that could play out, 893 00:59:53.840 --> 00:59:55.599 and you know, I may or may not be in 894 00:59:55.639 --> 00:59:58.320 a position to get my perfect wish. So my perfect 895 00:59:58.360 --> 01:00:03.800 wish is that we would do a partnership with a 896 01:00:03.880 --> 01:00:08.239 large pharma company, either a joint venture where we share 897 01:00:08.320 --> 01:00:12.079 responsibility for the further development, for the carrying out of 898 01:00:12.079 --> 01:00:14.480 the phase three, so that we could have influence over 899 01:00:14.519 --> 01:00:17.400 how the phase three is developed, what kind of patients 900 01:00:17.440 --> 01:00:19.880 it gets used, and how it's being tested so that 901 01:00:19.920 --> 01:00:22.159 they don't mess it up, that kind of thing. And 902 01:00:22.199 --> 01:00:24.519 then you know, going into the marketing, likely the big 903 01:00:24.559 --> 01:00:26.199 pharma company, we do all the marketing, and then we 904 01:00:26.239 --> 01:00:29.239 would get royalties from that. So we would get upfronts 905 01:00:29.280 --> 01:00:32.440 and royalties, likely in either the scenario where it was 906 01:00:32.480 --> 01:00:35.639 a joint venture or where we just sold the drug 907 01:00:35.920 --> 01:00:38.920 to a partner and they just took it over from there. 908 01:00:39.199 --> 01:00:41.400 And then you know, another possibility is that our whole 909 01:00:41.400 --> 01:00:44.760 company would get acquired by a large drug company. That's 910 01:00:45.320 --> 01:00:48.039 not really my favorite idea because what I really want 911 01:00:48.079 --> 01:00:51.679 to do is take the proceeds from that equity event 912 01:00:52.039 --> 01:00:53.840 when they buy the drug from us. So they do 913 01:00:53.880 --> 01:00:56.480 a deal and we get upfronts, and then we pour 914 01:00:56.880 --> 01:01:00.280 that money back into the company, into our platform so 915 01:01:00.280 --> 01:01:03.400 that we can develop our next ten drugs with those funds, 916 01:01:03.480 --> 01:01:06.039 which might not happen if we get acquired. 917 01:01:06.360 --> 01:01:10.519 Yes, indeed, I think it would be a preferable outcome 918 01:01:10.760 --> 01:01:16.079 if you continue to have input and involvement and an 919 01:01:16.119 --> 01:01:21.519 income stream from how that drug gets developed and used, 920 01:01:21.639 --> 01:01:26.280 in particular, because then you could ensure that it actually 921 01:01:26.280 --> 01:01:30.920 gets rolled out to patients. Sometimes pharmaceutical companies will acquire 922 01:01:30.960 --> 01:01:35.519 intellectual property and sit on it, and that's not necessarily 923 01:01:35.920 --> 01:01:41.679 the best outcome for patients who could benefit from the 924 01:01:41.760 --> 01:01:46.159 drug in clinical settings. Bill Wonders, would DP zero zero 925 01:01:46.199 --> 01:01:48.880 three qualify for fast track clinical studies. 926 01:01:49.039 --> 01:01:51.440 I think that to be fast track, it would have 927 01:01:51.480 --> 01:01:55.559 to be rare disease. I am envisioning it more angling 928 01:01:55.599 --> 01:02:01.960 towards accelerated approval, which is what FDA uses for disease indications, 929 01:02:02.039 --> 01:02:06.360 where you may be able to get a tentative approval 930 01:02:06.840 --> 01:02:09.719 and then need to keep doing studies to prove that 931 01:02:09.760 --> 01:02:12.840 you're having the outcome effects like effects on heart attacks 932 01:02:12.920 --> 01:02:15.599 or strokes. That's really my dream for this is that 933 01:02:15.679 --> 01:02:18.400 we would get approved on the basis of plaque regression, 934 01:02:19.039 --> 01:02:22.199 rather than doing what is traditionally done, which is due 935 01:02:22.280 --> 01:02:25.639 like a long five year study with thousands of patients 936 01:02:25.679 --> 01:02:28.599 waiting for people to have heart attacks and strokes, and 937 01:02:28.639 --> 01:02:30.960 then you count bodies and you see if people on 938 01:02:31.000 --> 01:02:34.679 the active group die less or have fewer heart attacks 939 01:02:34.880 --> 01:02:37.239 than the people on the placebo group, which I think 940 01:02:37.320 --> 01:02:39.159 is we're going to look back on those kinds of 941 01:02:39.199 --> 01:02:42.079 studies someday and think they're barbaric. I hope that we 942 01:02:42.199 --> 01:02:45.559 can get accelerated approval on the basis of their plaque 943 01:02:45.599 --> 01:02:49.039 regression and then show the reduction in heart attacks and 944 01:02:49.079 --> 01:02:53.159 strokes in the following years after initial approval. 945 01:02:53.320 --> 01:02:57.559 Yes, indeed, that would definitely be more humane and better 946 01:02:57.599 --> 01:03:00.800 for the patients. So I know we're past the hour. 947 01:03:00.920 --> 01:03:03.280 Do you have time for a couple more questions just 948 01:03:03.360 --> 01:03:04.880 the ones that have been post? 949 01:03:05.039 --> 01:03:07.239 Let's say two more

questions and then I got to run. 950 01:03:07.800 --> 01:03:13.039 All right, So, Daniel Wonders, is the Victorian Hard Institute 951 01:03:13.079 --> 01:03:16.719 funding most or all of the trials now taking place. 952 01:03:17.199 --> 01:03:21.159 No, Cyclarity Therapeutics is funding one hundred percent of the 953 01:03:21.800 --> 01:03:25.880 trials taking place. Almost all of the money has come 954 01:03:25.920 --> 01:03:29.000 from private investment into Cyclarity therapeutics. 955 01:03:29.280 --> 01:03:29.719 All right. 956 01:03:30.119 --> 01:03:34.159 And Daniel's comment, after which I will pose his last question, 957 01:03:34.239 --> 01:03:37.119 is this is almost like a precursor to what cellular 958 01:03:37.239 --> 01:03:40.920 nanomachines might one day accomplish and I hope we all 959 01:03:41.199 --> 01:03:44.880 live to see the day when that happens. And his 960 01:03:45.039 --> 01:03:49.079 final question is he sees that it's interesting that the 961 01:03:49.599 --> 01:03:54.840 blockbuster drug Britian out sells the anesthesia drugs or did 962 01:03:54.880 --> 01:03:59.079 he hear that incorrectly? Does it actually outsell the common 963 01:03:59.119 --> 01:03:59.960 anesthesia drug. 964 01:04:01.159 --> 01:04:05.400 Yeah, it outsells all of anesthesia put together. Now that said, 965 01:04:05.559 --> 01:04:10.400 that's a little bit misleading because Britian is still unpatent 966 01:04:10.599 --> 01:04:13.400 and so Merk can charge a lot of money for it, 967 01:04:13.440 --> 01:04:17.719 whereas most traditionally used anesthesia agents are generic and pretty cheap. 968 01:04:17.760 --> 01:04:20.840 But it's still pretty impressive to me that this one 969 01:04:21.199 --> 01:04:27.000 reversal agent, it's so incredibly valuable and profitable because anesthesiologists 970 01:04:27.119 --> 01:04:31.719 love it. It's incredibly safe and effective, and even if 971 01:04:31.719 --> 01:04:35.800 they accidentally were on purpose, anesthesiologists are getting lazy and 972 01:04:36.400 --> 01:04:40.679 dosing their patients with an excess of Britian. And I 973 01:04:40.760 --> 01:04:43.719 was a study done recently trying to bring them to 974 01:04:43.800 --> 01:04:49.280 task and looking for the consequences of giving your patients 975 01:04:49.320 --> 01:04:53.239 too much Britian, and they couldn't find any consequences from 976 01:04:53.239 --> 01:04:56.480 giving patients, like you know, two or three times as 977 01:04:56.519 --> 01:04:59.760 much Britian as they needed to clear out the paralytics. 978 01:05:00.639 --> 01:05:03.400 The anesthesiologists are just strigging their shoulders and like not 979 01:05:03.480 --> 01:05:05.519 doing the math to figure out exactly how much they 980 01:05:05.519 --> 01:05:08.199 should give their patients and just taking a you know, 981 01:05:08.239 --> 01:05:10.039 a bunch off of the shelf and giving them the 982 01:05:10.039 --> 01:05:13.039 whole bial rather than calculating how much they should be 983 01:05:13.079 --> 01:05:16.000 getting their patient. Because it's it's a next generation drug. 984 01:05:16.039 --> 01:05:19.239 It only grabs onto something bad that you want to 985 01:05:19.280 --> 01:05:22.239 get rid of and then you pee it out and 986 01:05:22.280 --> 01:05:24.639 you pee out you know, whatever extra that you that 987 01:05:24.719 --> 01:05:27.920 you get. So it's really a perfect drug, and you 988 01:05:27.960 --> 01:05:30.320 know that's that's how we want our drug to work 989 01:05:30.360 --> 01:05:30.760 as well. 990 01:05:31.480 --> 01:05:34.719 Yes, that sounds like a great drug essentially no adverse 991 01:05:34.719 --> 01:05:38.400 side effects. So thank you Matthew for all of your 992 01:05:38.440 --> 01:05:41.679 answers and for your time today. That was a fascinating 993 01:05:41.719 --> 01:05:46.519 and enlightening presentation. Do you have any final words for 994 01:05:46.800 --> 01:05:50.519 our audience, any comments that you wish you could have made, 995 01:05:50.800 --> 01:05:53.559 or anything else that you want to say before we close. 996 01:05:54.880 --> 01:05:57.360 I just want to say thanks so much for having 997 01:05:57.400 --> 01:06:00.960 me here to present to the transhuman to a party 998 01:06:01.119 --> 01:06:05.079 and people have more ideas, you know, whether they're about 999 01:06:05.079 --> 01:06:08.039 the name, or about the science, or if you're in 1000 01:06:08.079 --> 01:06:11.440 science and you want to collaborate with Cyclarity, if you 1001 01:06:11.440 --> 01:06:13.440 know you're in a research lab and do you have 1002 01:06:13.480 --> 01:06:15.679 a model system that you think our drug could work in, 1003 01:06:15.719 --> 01:06:18.239 we'd love to collaborate with you and get to the 1004 01:06:18.239 --> 01:06:23.079 finish line together. It takes a huge number of people 1005 01:06:23.199 --> 01:06:27.440 to get a drug approved, and there's so many wonderful 1006 01:06:27.559 --> 01:06:31.719 supporters out there, and I invite everyone to get in touch, 1007 01:06:32.039 --> 01:06:34.800 get in touch with me on LinkedIn, follow up Cyclarity 1008 01:06:34.840 --> 01:06:37.880 on social media, and we'll try to keep you all 1009 01:06:37.960 --> 01:06:39.199 updated on how things are going. 1010 01:06:40.360 --> 01:06:43.760 All right, thank you very much, Okay for your time today. 1011 01:06:44.000 --> 01:06:48.000 This was quite an enlightening presentation. Please to all of 1012 01:06:48.079 --> 01:06:53.360 our viewers, share your ideas with us in the chat 1013 01:06:53.519 --> 01:06:57.719 or reach out to ok and to Cyclarity on social media. 1014 01:06:57.840 --> 01:07:01.280 And I hope that we can all live long and prosper. 1015 01:07:05.360 --> 01:07:05.800 Thank you. 1016 01:07:06.400 --> 01:07:12.760 Indeed, thanks Cody and Ghanadi. We want to get rid 1017 01:07:12.800 --> 01:07:16.880 of this guy. As you know, our purpose here at 1018 01:07:16.880 -->

01:07:24.719 Redfast Revolution against Agent and Death is to kill death. Right, So, uh, Joe, 1019 01:07:25.440 --> 01:07:26.480 how are we going. 1020 01:07:26.360 --> 01:07:26.960 To kill death? 1021 01:07:27.800 --> 01:07:29.480 I mean together, that's the whole thing. 1022 01:07:30.559 --> 01:07:36.880 Together together in a coordinated, collaborative fashion where we feel 1023 01:07:37.280 --> 01:07:39.960 like we feel we feel our life more than we 1024 01:07:40.000 --> 01:07:40.360 feel that. 1025 01:07:42.239 --> 01:07:45.480 Okay, and Cody, how are we going to kill death? 1026 01:07:45.519 --> 01:07:47.840 How is it I mortally is going to kill death? 1027 01:07:47.960 --> 01:07:50.320 Well, everything Joe just said. But also we need to 1028 01:07:50.360 --> 01:07:52.920 free the geniuses of society who are working on the 1029 01:07:52.960 --> 01:07:55.599 science end of it, and we do that together. 1030 01:07:57.559 --> 01:07:59.960 Good, So, Ghannadi tell us your view. 1031 01:08:00.760 --> 01:08:04.039 We need to get the public to recognize that killing 1032 01:08:04.119 --> 01:08:08.000 death is both feasible and desirable. They need to see 1033 01:08:08.039 --> 01:08:12.400 a plausible path for getting from here to there, and 1034 01:08:12.440 --> 01:08:16.039 that's actually one way in which games like lev the 1035 01:08:16.119 --> 01:08:18.640 Game can help to get them to see it's not 1036 01:08:18.720 --> 01:08:21.239 going to be a single moment in time. It's not 1037 01:08:21.279 --> 01:08:24.359 going to be a single magic pill or panacee. It's 1038 01:08:24.359 --> 01:08:27.079 going to be a process. But it's a process that 1039 01:08:27.600 --> 01:08:30.720 each person, even if you're sixty five or seventy five 1040 01:08:30.840 --> 01:08:35.640 or eighty or ninety, has a chance in undergoing successfully. 1041 01:08:37.319 --> 01:08:42.840 Okay, I will play Devil's advocate and I will ask Death, Death, 1042 01:08:42.960 --> 01:08:44.079 what did you think about that? 1043 01:08:44.880 --> 01:08:48.920 I was quite inspired by Joe's talk, and it's been 1044 01:08:49.079 --> 01:08:53.079 quite lonely as the only ageless character. Maybe you should 1045 01:08:53.159 --> 01:08:53.960 join them. 1046 01:08:54.640 --> 01:08:59.039 Wow, that's good. That's good. Uh, but uh, how about 1047 01:08:59.119 --> 01:09:00.079 if we killed you? 1048 01:09:01.359 --> 01:09:05.399 That would not be pleasant at all? Although I am 1049 01:09:05.520 --> 01:09:08.039 so busy of late, I could use the rest. 1050 01:09:09.560 --> 01:09:10.520 Ah. Good. 1051 01:09:10.680 --> 01:09:14.159 At least we could freeze you. Okay, we can keep 1052 01:09:14.239 --> 01:09:15.680 you frozen forever. 1053 01:09:16.520 --> 01:09:18.119 That would be quite peaceful. 1054 01:09:19.119 --> 01:09:21.680 But I think you like more the hit than the cold. 1055 01:09:21.720 --> 01:09:22.600 What do you like more? 1056 01:09:23.399 --> 01:09:25.920 The cold is quite fine. These bonds don't care. 1057 01:09:27.840 --> 01:09:32.000 Okay, Before we sacrifice death, is there a question from 1058 01:09:32.039 --> 01:09:33.520 the public to death? 1059 01:09:35.720 --> 01:09:35.760 No? 1060 01:09:39.000 --> 01:09:41.399 I like that, that's a good question. What is your 1061 01:09:41.479 --> 01:09:41.960 last male? 1062 01:09:42.560 --> 01:09:43.840 I prefer souls? 1063 01:09:45.279 --> 01:09:52.359 Okay, we have a question here also ruddy No, okay, 1064 01:09:52.640 --> 01:09:56.079 So why don't you come in front death here and 1065 01:09:56.159 --> 01:09:57.760 see how we can sacrifice you? 1066 01:10:02.319 --> 01:10:06.640 So I grab that we are all going to punch 1067 01:10:06.720 --> 01:10:07.960 him Halloween. 1068 01:10:09.159 --> 01:10:09.680 Halloween. 1069 01:10:10.399 --> 01:10:14.520 So yeah, we. 1070 01:10:14.479 --> 01:10:17.439 Are here to kill death before death kills us. So 1071 01:10:18.000 --> 01:10:30.800 for immortality, Viva Revolution, Viva. Okay, now, Death you can go, 1072 01:10:33.319 --> 01:10:36.920 and let's go for the questions. How we want people? 1073 01:10:37.159 --> 01:10:40.760 This is a fantastic panel. We have incredible people working 1074 01:10:40.800 --> 01:10:43.880 on different projects. I'm so excited to be here. This 1075 01:10:43.920 --> 01:10:50.800 is our family. So questions from our family members, Okay, 1076 01:10:50.920 --> 01:10:53.199 all the way, Okay, first one that is closer. 1077 01:10:54.079 --> 01:10:56.000 This is a This is more of a just an observation. 1078 01:10:57.039 --> 01:11:00.680 I thought the points you made, Joe were just truly 1079 01:11:00.720 --> 01:11:04.760 deep and profound and hit me in my heart. I 1080 01:11:04.840 --> 01:11:08.640 think all of us struggle with various things and including 1081 01:11:09.560 --> 01:11:12.680 lack of influence and frustration and ego and all that. 1082 01:11:13.399 --> 01:11:20.039 But if we can collaborate and basically put our private 1083 01:11:20.119 --> 01:11:24.720 concerns aside and think bigger and think real, longer range, 1084 01:11:24.960 --> 01:11:25.920 we'll all be better off. 1085 01:11:25.960 --> 01:11:26.760 So thank you for that. 1086 01:11:27.159 --> 01:11:32.159 Yeah, we're I mean a lot of people in this room, 1087 01:11:32.199 --> 01:11:34.720 a lot of people. The people who put rat Fest 1088 01:11:34.800 --> 01:11:38.520 together are from people unlimited and and we sort of 1089 01:11:38.520 --> 01:11:41.119 have we have the strength and the focus to do 1090 01:11:41.199 --> 01:11:43.680 that because we have we have one another. 1091 01:11:43.960 --> 01:11:46.359 Okay, so we're not working. We're not solo agents. 1092 01:11:46.640 --> 01:11:49.640 It's it's tough to be a solo agent immortalist in 1093 01:11:49.920 --> 01:11:50.880 you know, in this world. 1094 01:11:52.279 --> 01:11:54.319 Okay, we have a question here in the bank. 1095 01:11:55.840 --> 01:11:56.479 Thank you, Jove. 1096

01:11:57.000 --> 01:12:00.920 He's very inspiring to hear you all the time. Understanding 1097 01:12:01.239 --> 01:12:08.880 human being unbelievable. I treasure you. You talked recently about 1098 01:12:09.439 --> 01:12:12.239 he's going to need a new faith. That touched me 1099 01:12:12.560 --> 01:12:17.239 very deeply. Can you explain a little bit to the audience, Well, 1100 01:12:17.319 --> 01:12:19.119 you mean by having this new faith. 1101 01:12:19.199 --> 01:12:21.680 Yeah, I think I think, Uh, a lot of us 1102 01:12:22.079 --> 01:12:24.840 have felt like, oh, something was gonna happen, there's gonna 1103 01:12:24.840 --> 01:12:31.520 be a particular breakthrough before now, and have gotten discouraged. 1104 01:12:32.079 --> 01:12:35.279 Horrible things happened. I lost Bernie. I mean, that's the 1105 01:12:35.319 --> 01:12:36.680 fucking worst thing that can happen. 1106 01:12:38.600 --> 01:12:41.159 And and uh, and. 1107 01:12:41.159 --> 01:12:44.239 So these there's a faith that's basically we're externalizing. 1108 01:12:45.039 --> 01:12:45.319 Uh. 1109 01:12:45.359 --> 01:12:46.680 And this is the faith we learn it. 1110 01:12:46.720 --> 01:12:49.359 We actually learned this from religion, which is really we're 1111 01:12:49.399 --> 01:12:50.920 like and I mean to. 1112 01:12:52.439 --> 01:12:52.760 We do. 1113 01:12:53.439 --> 01:12:55.840 But but even if even if you're keep your religion, 1114 01:12:55.880 --> 01:12:59.159 we're we have we have to modify. Okay, we have to. 1115 01:12:59.239 --> 01:13:02.079 We have to develop here. And and so there's a 1116 01:13:02.119 --> 01:13:04.880 faith that's innate. It's innate to the human body. It's 1117 01:13:04.920 --> 01:13:08.079 a feeling of it's a feeling, a core gut feeling 1118 01:13:08.319 --> 01:13:11.000 of life. It's not really it's not really dependent on 1119 01:13:11.039 --> 01:13:13.960 what's happening out here. It's not really dependent on is 1120 01:13:14.000 --> 01:13:16.840 this breakthrough gonna happen, Is this piece of funding gonna happen? 1121 01:13:17.079 --> 01:13:19.640 It's it is what is It's not faith that's just 1122 01:13:19.760 --> 01:13:22.880 core in our bodies. That is it's not part of 1123 01:13:22.880 --> 01:13:25.439 our mentality. We're not really, we can't really measure it. 1124 01:13:25.640 --> 01:13:28.560 We're not really, we're not. It's not dependent on anything 1125 01:13:29.079 --> 01:13:32.000 out here, because good things happen and bad things happen. 1126 01:13:32.560 --> 01:13:36.000 And that's how we keep going because we just because it, 1127 01:13:36.199 --> 01:13:39.640 because it's it's something physical, it's something I wish Rose 1128 01:13:39.680 --> 01:13:41.600 was here. Michael Rose, you probably have something to say 1129 01:13:41.600 --> 01:13:44.520 about it, because it's something innate to the human form 1130 01:13:44.680 --> 01:13:47.760 that we're tapping into. That isn't it's not doctrinaire, it's 1131 01:13:47.840

--> 01:13:48.560 just organic. 1132 01:13:52.159 --> 01:13:52.560 Okay. 1133 01:13:52.640 --> 01:13:56.159 We have balloons for the people with questions. Uh it 1134 01:13:56.279 --> 01:13:59.960 says a stop agent in Spanish, stop and be simeon. 1135 01:14:00.439 --> 01:14:03.880 So you have a question or you one double or both? 1136 01:14:07.119 --> 01:14:10.840 What can we do? What can we do to. 1137 01:14:12.399 --> 01:14:17.000 Double this attendance of Bradfest this year, double it again 1138 01:14:17.079 --> 01:14:20.479 next year, double again, keep doubling it every year. 1139 01:14:22.840 --> 01:14:27.359 Yes, thank you. We need help. We need we need help. 1140 01:14:27.359 --> 01:14:29.159 We work our asses off. We have some We have 1141 01:14:29.159 --> 01:14:31.079 about seven hudred registrations here. It's a little bit more 1142 01:14:31.119 --> 01:14:34.319 than last year, which is which is nice. But but 1143 01:14:34.319 --> 01:14:36.199 but that's really what we want to do. That really 1144 01:14:36.279 --> 01:14:40.640 is our vision and and and we need help, like 1145 01:14:40.680 --> 01:14:44.800 we need we need other organizations to to see this 1146 01:14:45.000 --> 01:14:49.159 vision and and and share this share this opportunity with us, 1147 01:14:49.279 --> 01:14:50.800 and we need people to do it. We need people 1148 01:14:50.800 --> 01:14:52.720 to bring people and we say this every year and 1149 01:14:52.720 --> 01:14:56.279 and and the truth is it doesn't happen. So so 1150 01:14:56.279 --> 01:14:58.680 so we just shift in mindset. And I mean part 1151 01:14:58.680 --> 01:15:00.319 of it is just me being more direct, like I 1152 01:15:00.359 --> 01:15:02.800 am here. I don't think we've been this direct, but. 1153 01:15:03.800 --> 01:15:05.439 We need help. You know, people come up to us 1154 01:15:05.439 --> 01:15:06.720 and we're gonna help, We're gonna do it. 1155 01:15:06.760 --> 01:15:09.079 And a lot of times they're marketers and they're just 1156 01:15:09.119 --> 01:15:11.680 selling us their services. That's not really what I'm talking about. 1157 01:15:11.840 --> 01:15:14.720 I'm talking about like, I'm talking about people who want 1158 01:15:14.760 --> 01:15:18.000 to who want to share this vision and this mission 1159 01:15:18.039 --> 01:15:21.119 with us. Yeah, because it's for everybody. 1160 01:15:20.720 --> 01:15:24.079 Actually, Okay, okay, here another question in the front. 1161 01:15:24.800 --> 01:15:29.039 Yes, So this room is full of change agents. 1162 01:15:29.600 --> 01:15:29.840 Right. 1163 01:15:31.159 --> 01:15:35.399 When I work to create the Health Spent Action Coalition, 1164 01:15:36.119 --> 01:15:40.840 which as two hundred and seventy five cross sector organizations, 1165 01:15:41.319 --> 01:15:46.000 I worked with a wonderful operator that helped manage Props 1166 01:15:46.039 --> 01:15:49.479 seventy one and Prop fourteen and got fifteen billion dollars 1167 01:15:49.520 --> 01:15:54.199 of California taxpayer money for an agency for regenerative medicine. 1168 01:15:54.760 --> 01:15:59.479 That was the work of advocates, and that was the 1169 01:15:59.520 --> 01:16:05.720 work of narratives of people, right, narratives of people. So 1170 01:16:05.880 --> 01:16:08.600 before I took this on as a stem cell advocate, 1171 01:16:08.600 --> 01:16:12.560 in the background in law, a person that inspired me 1172 01:16:13.319 --> 01:16:18.079 was a young woman, Sabrina Cohen. She became a quadriplegic 1173 01:16:18.119 --> 01:16:21.199 and an accident when fourteen years old from Miami Beach. 1174 01:16:21.239 --> 01:16:24.119 I met her at the Miami Project to Cure Paralysis 1175 01:16:24.159 --> 01:16:26.960 when I was giving a talk. She looked just like 1176 01:16:27.079 --> 01:16:31.359 Sandra Bullock in a wheelchair. She became the first associate 1177 01:16:31.439 --> 01:16:35.399 director of my organization, a nonprofit organization that created the 1178 01:16:35.399 --> 01:16:40.000 World stem Cell Summit, and before we launched the health 1179 01:16:40.039 --> 01:16:44.560 Span Action Coalition, which was founded on an idea between 1180 01:16:44.600 --> 01:16:48.159 Aubrey and I to bring this world together. Health span 1181 01:16:48.279 --> 01:16:52.720 should be a fundamental human right. I asked Sabrina, who 1182 01:16:52.760 --> 01:16:57.119 has gone on in a top realtor and created Sabrina 1183 01:16:57.159 --> 01:17:03.520 Cohen Foundation Adaptive Beach Days in Miami. Each Sabrina does immortality. 1184 01:17:03.680 --> 01:17:08.279 Does a long life, a long lifespan matter to people 1185 01:17:08.399 --> 01:17:15.520 in your community, meaning the sci spinal cord injury community. Yes, Bernie, 1186 01:17:15.800 --> 01:17:20.399 we in our community know we're aging faster, We know 1187 01:17:20.640 --> 01:17:23.359 we are going to die young for all the things 1188 01:17:23.359 --> 01:17:26.600 that we go through day by day. And I will 1189 01:17:26.760 --> 01:17:30.800 join you and the spinal cord injury world will do 1190 01:17:30.880 --> 01:17:34.560 it be a part of this. This is cross sector 1191 01:17:35.159 --> 01:17:38.760 and it's and you are the spark. I mean, I 1192 01:17:38.800 --> 01:17:41.560 am really inspired by being here. I was nervous about 1193 01:17:41.560 --> 01:17:44.359 coming to this because I heard about Ratfest and it 1194 01:17:44.439 --> 01:17:47.079 might be like a rave and you know grave, you know, 1195 01:17:47.439 --> 01:17:49.680 but this is really the real deal. So I just 1196 01:17:49.720 --> 01:17:53.439 want to say how inspired I am and proud to 1197 01:17:53.479 --> 01:17:54.640 be associated with. 1198 01:17:54.600 --> 01:18:01.920 You and Barney those words coming from you are very 1199 01:18:02.000 --> 01:18:04.439 important to all of us, huh and all you have 1200 01:18:04.560 --> 01:18:05.680 been doing for so long. 1201 01:18:06.239 --> 01:18:10.399 So okay, yes, First of

all, Bernie, I'd like to 1202 01:18:10.760 --> 01:18:14.680 thank you for the heroic work that you and Melissa 1203 01:18:14.800 --> 01:18:19.359 King have done over the decades and advocating for stem 1204 01:18:19.439 --> 01:18:24.640 cell research, which is a crucial pathway toward life extension 1205 01:18:25.079 --> 01:18:28.640 and curing deadly diseases that could kill people in the meantime. 1206 01:18:29.039 --> 01:18:32.920 And I also wanted to echo what you said in 1207 01:18:33.000 --> 01:18:38.319 terms of encouraging people to find initiatives that already exist 1208 01:18:38.479 --> 01:18:41.760 that they could contribute to And this also goes along 1209 01:18:41.760 --> 01:18:47.039 the lines of what Joe articulated, because even when I 1210 01:18:47.079 --> 01:18:49.319 was looking out to see how I could contribute to 1211 01:18:49.359 --> 01:18:52.960 the field, I was thinking about what endeavors were already 1212 01:18:53.079 --> 01:18:57.960 in progress that needed help. And you are important, as 1213 01:18:58.039 --> 01:19:01.439 Joe said, one person can make a difference within that 1214 01:19:01.560 --> 01:19:05.479 collaborative approach. Like with led the game, I saw that 1215 01:19:05.520 --> 01:19:08.439 there was a previous team that had tried to develop 1216 01:19:08.479 --> 01:19:11.079 it but didn't have the funds, and I didn't want 1217 01:19:11.079 --> 01:19:13.479 that project to just languish. I didn't want it to 1218 01:19:13.560 --> 01:19:16.880 disappear down the memory hole, since there wasn't even the 1219 01:19:16.920 --> 01:19:20.479 source code for the original game remaining. So I brought 1220 01:19:20.479 --> 01:19:23.760 it to a playable state. But I needed another individual 1221 01:19:23.840 --> 01:19:26.840 Y'ari starin Vukotich to program it. I needed the community 1222 01:19:26.880 --> 01:19:31.600 to provide feedback. Likewise with the Transhumanist Party, when Zoltenischwan 1223 01:19:31.920 --> 01:19:34.920 founded it, he ran for president. He had the Immortality 1224 01:19:34.920 --> 01:19:39.119 Bus campaign. In twenty sixteen, he decided he wanted to 1225 01:19:39.159 --> 01:19:42.119 move on to other endeavors, so he stepped down from 1226 01:19:42.119 --> 01:19:45.159 the leadership role of the Transhumanist Party. Really, he's more 1227 01:19:45.239 --> 01:19:49.279 like a serial startup founder than someone who keeps an 1228 01:19:49.319 --> 01:19:52.239 initiative going for years, but he wanted it to go 1229 01:19:52.319 --> 01:19:55.479 on for years. He wanted it to outlast his tenure. 1230 01:19:55.560 --> 01:19:58.600 So he asked me to be the chairman, and I decided, well, 1231 01:19:58.840 --> 01:20:02.680 this is my opportunity to contribute to something longer lasting 1232 01:20:02.720 --> 01:20:05.199 and perhaps something that would last beyond my own tenure 1233 01:20:05.479 --> 01:20:08.600 as chairman. So think about those kinds of initiatives, those 1234 01:20:08.640 --> 01:20:11.239 that are already in progress that you could make a 1235 01:20:11.279 --> 01:20:13.680 difference and you could carry to the next level. 1236 01:20:15.520 --> 01:20:18.960 Okay, good point, eleanor a balloon, I'm a question. 1237 01:20:19.640 --> 01:20:22.760 I want I want to ask the question for the balloon, 1238 01:20:22.840 --> 01:20:25.920 So thank you so much. No, but so you were talking, 1239 01:20:26.000 --> 01:20:31.800 Joe about numbers matter and which is true, but there's 1240 01:20:31.800 --> 01:20:36.159 something about passion and having such a conviction of moving 1241 01:20:36.199 --> 01:20:39.000 this initiative forward, and I was wondering, if you this 1242 01:20:39.039 --> 01:20:41.800 is a good time maybe to tell all these activists 1243 01:20:41.840 --> 01:20:46.199 here what it takes to create Radfist and how even 1244 01:20:46.479 --> 01:20:48.880 one more person that jumps in in the way that 1245 01:20:48.920 --> 01:20:51.840 they can contribute can make a difference, because I don't 1246 01:20:51.880 --> 01:20:54.960 know if people here know what kind of team you 1247 01:20:55.000 --> 01:20:59.560 guys have and how long it takes to actually produce 1248 01:20:59.640 --> 01:21:01.840 this of So maybe you can give a little bit 1249 01:21:01.840 --> 01:21:02.720 of detail. 1250 01:21:03.079 --> 01:21:08.840 Yeah, we have a really small, really good team. Uh 1251 01:21:09.319 --> 01:21:12.399 of I want to say, you know, Michelle Andrews uh, 1252 01:21:12.760 --> 01:21:19.119 Jeene Wideman, uh, Marianna Cellis and Daniella Escobar is the 1253 01:21:19.159 --> 01:21:23.000 team with Jim and I and you know they're working 1254 01:21:23.039 --> 01:21:27.039 on that, uh you know, most of the year, most 1255 01:21:27.079 --> 01:21:34.680 of the year and so so. But but the vision 1256 01:21:34.720 --> 01:21:38.079 is of a platform, and that's and that's where we 1257 01:21:38.119 --> 01:21:41.960 can do something that doesn't really have a limit in 1258 01:21:42.079 --> 01:21:45.960 size and and we basically do it on like a 1259 01:21:46.079 --> 01:21:51.479 zero budget. Like we basically do it on on uh 1260 01:21:51.760 --> 01:21:55.199 there's there's no extra money in this, so we you know, 1261 01:21:55.800 --> 01:21:58.359 and and Jim doesn't get paid, you know, and I 1262 01:21:58.359 --> 01:21:59.279 get paid a little bit. 1263 01:21:59.600 --> 01:21:59.800 You know. 1264 01:22:00.039 --> 01:22:03.479 That's why I'm doing uh uh messaging strategy for you know, 1265 01:22:03.520 --> 01:22:06.199 boring companies, but which I try to help them. 1266 01:22:06.279 --> 01:22:09.439 But yeah, so so. 1267 01:22:11.720 --> 01:22:13.199 And this is a little bit, this is a little 1268 01:22:13.199 --> 01:22:15.399 bit where we are because because we're on the cutting 1269 01:22:15.479 --> 01:22:18.159 edge of longevity, right, I mean that's and and this 1270 01:22:18.239 --> 01:22:21.319 is where this is where the space is

right now 1271 01:22:21.520 --> 01:22:24.159 and it doesn't need to be like we could have 1272 01:22:24.359 --> 01:22:29.239 we could have volunteers that have superb capability that could really, 1273 01:22:29.359 --> 01:22:32.600 as you're saying, really expand what we're doing. We could 1274 01:22:32.640 --> 01:22:34.199 have a chunk of money that isn't even that big 1275 01:22:34.199 --> 01:22:36.760 of a chunk of money that could change how we 1276 01:22:36.800 --> 01:22:42.199 function so so and it's time for that. Honestly, it's 1277 01:22:42.239 --> 01:22:44.479 time for that. So you guys love rat Fest. We 1278 01:22:44.520 --> 01:22:48.439 love rat Fest, but you know we don't honestly, we 1279 01:22:48.439 --> 01:22:49.880 don't want to keep just doing it like this. 1280 01:22:50.880 --> 01:22:51.319 We don't. 1281 01:22:51.439 --> 01:22:54.720 We we we we we want it. We have to 1282 01:22:54.760 --> 01:22:58.920 go uh in a more. I want to say bigger, 1283 01:22:58.960 --> 01:23:00.880 but it's not just about bigger. It's it's just an 1284 01:23:00.880 --> 01:23:04.439 ex we have to expand. That's that's, that's what has 1285 01:23:04.479 --> 01:23:04.880 to happen. 1286 01:23:05.399 --> 01:23:09.399 I add that one person with a passion is more 1287 01:23:09.479 --> 01:23:12.760 powerful than one hundred people with an interest. So whatever 1288 01:23:12.800 --> 01:23:15.880 we can do to increase passion in ourselves, we need 1289 01:23:15.920 --> 01:23:17.680 to do that. And we need to bring more people 1290 01:23:17.760 --> 01:23:20.319 in who have passion more so than interest. 1291 01:23:23.399 --> 01:23:28.199 Yeah, just let me add we need to collaborate internationally. 1292 01:23:28.600 --> 01:23:30.960 Like for example, I'm very happy that every year I 1293 01:23:31.039 --> 01:23:34.680 bring friends. In fact, here is a Spanish friend Elena, 1294 01:23:35.319 --> 01:23:39.199 and there is as a Mexican friend Dorris, and then 1295 01:23:39.399 --> 01:23:40.279 also Cody. 1296 01:23:40.920 --> 01:23:42.279 Cody always brings friends. 1297 01:23:42.319 --> 01:23:46.319 We have Mark Hamilton, we have well as behind all 1298 01:23:46.359 --> 01:23:47.279 of us bring people. 1299 01:23:47.319 --> 01:23:48.479 We need to bring more people. 1300 01:23:48.520 --> 01:23:51.119 We need to collaborate, and we need to keep this 1301 01:23:51.520 --> 01:23:56.159 growing growing, and also in different places. Because I organize 1302 01:23:56.199 --> 01:23:59.840 something in Spain as well. On my public is mostly 1303 01:24:00.000 --> 01:24:03.000 Spanish and then some of those come here as well. 1304 01:24:03.560 --> 01:24:07.359 So we need to keep on collaborating and also experiment 1305 01:24:07.439 --> 01:24:11.800 different things like we are doing this march in the 1306 01:24:11.880 --> 01:24:14.439 Centers of Power of Spain. That is why I think 1307 01:24:14.479 --> 01:24:17.000 it's so important that we have a rally for Longevity 1308

01:24:17.000 --> 01:24:17.840 in Washington, d C. 1309 01:24:18.520 --> 01:24:20.239 Washington d C has to see this. 1310 01:24:20.880 --> 01:24:27.279 As Gennadi mentioned the Immortality Bones the coffin, it was 1311 01:24:27.279 --> 01:24:31.359 a coffin in front of the US Capitol that actually 1312 01:24:31.359 --> 01:24:35.239 should have had more media coverage. And you know, the 1313 01:24:35.359 --> 01:24:39.520 Coalition for Radical Eve Extension can do it and better 1314 01:24:40.079 --> 01:24:45.199 because I like Sultan Isban, but it was one man show. 1315 01:24:45.840 --> 01:24:49.279 Here we are hundreds of people from all over the world. 1316 01:24:49.760 --> 01:24:53.600 And then before giving you the word gym, because there 1317 01:24:53.600 --> 01:24:55.479 are other initiatives we need to adapt. 1318 01:24:55.640 --> 01:24:56.479 And I want. 1319 01:24:56.279 --> 01:25:00.640 To ask, because Cody hasn't spoken too much, where we 1320 01:25:00.680 --> 01:25:03.199 are going to be next month and what we are 1321 01:25:03.239 --> 01:25:04.359 going to do next month. 1322 01:25:05.239 --> 01:25:07.359 Yeah, let me let me just jump in just quickly. Look, 1323 01:25:10.119 --> 01:25:16.079 we're not just like immortality entrepreneurs. We're not just like 1324 01:25:16.560 --> 01:25:19.600 starting something and moving on to the next thing. 1325 01:25:20.039 --> 01:25:22.840 That's not what we're doing. We're we're we're. 1326 01:25:22.520 --> 01:25:24.680 In this and we're not going to quit on this, 1327 01:25:24.760 --> 01:25:26.439 and we're actually not going to quit on you. 1328 01:25:26.960 --> 01:25:28.560 And that's the difference. You know. 1329 01:25:29.520 --> 01:25:31.840 It's it's one thing to have a campaign and do 1330 01:25:31.920 --> 01:25:34.680 something and then disappear into something else. That's not what 1331 01:25:34.840 --> 01:25:37.760 That's not what we're about. We're we're on this and 1332 01:25:37.800 --> 01:25:40.079 I and we've shown that because ten years is ten years. 1333 01:25:40.239 --> 01:25:43.720 We're we're we're on this to stay. That's that's why, honestly, 1334 01:25:43.760 --> 01:25:44.960 that's why you should support us. 1335 01:25:45.319 --> 01:25:48.199 Well, we are here to kill death. Look at it 1336 01:25:48.399 --> 01:25:50.800 death there. We are here to kill you. 1337 01:25:51.720 --> 01:25:52.000 Uh. 1338 01:25:52.039 --> 01:25:55.000 And there are different approaches. So so what are we 1339 01:25:55.079 --> 01:25:57.359 going to do? Who are we going to meet where? 1340 01:25:57.399 --> 01:25:57.760 Cody? 1341 01:25:58.119 --> 01:26:01.680 Okay, Well, first I wanted to say, Immortalis is kind 1342 01:26:01.680 --> 01:26:05.039 of doing slightly what Radfast is doing, but on a 1343 01:26:05.039 --> 01:26:08.840 different stage. So Radfest gives the scientists and the researchers 1344 01:26:08.840 --> 01:26:12.359 of longevity the stage and the voice to the public 1345 01:26:12.720 --> 01:26:16.039 and immortalis is giving the stage to those same people 1346 01:26:16.399 --> 01:26:20.760 to move forward faster and what they're doing. So next 1347 01:26:20.840 --> 01:26:23.520 month we are going with jose To. He's going to 1348 01:26:23.600 --> 01:26:27.159 introduce us to one of his friends in Argentina, Javier Malay. 1349 01:26:27.199 --> 01:26:30.239 The President of Argentina, is going to meet with us 1350 01:26:30.720 --> 01:26:35.279 with Mark Wallas, I mean Mark Hamilton Wallas and Cody 1351 01:26:35.359 --> 01:26:40.239 and myself because we are proposing to have Immortalists in 1352 01:26:40.560 --> 01:26:44.119 Buenos Aires, south of Buenos Aires, and we want competition. 1353 01:26:44.359 --> 01:26:46.640 Also the USA has to get in there. Of course, 1354 01:26:46.680 --> 01:26:47.920 the USA has to be there. 1355 01:26:48.359 --> 01:26:51.520 Argentina is one of three or four governments we're in 1356 01:26:51.560 --> 01:26:52.520 talks with right now. 1357 01:26:54.359 --> 01:26:59.079 So okay, Jim here is the father of the beast. 1358 01:27:00.359 --> 01:27:01.079 Thank you. I'll thank you. 1359 01:27:01.119 --> 01:27:03.119 A great job. You guys, great John, thank you, thank 1360 01:27:03.119 --> 01:27:05.720 you all of it. You're great, You're fantastic. I just 1361 01:27:05.720 --> 01:27:08.079 want to make one thing simple here that I'm feeling 1362 01:27:08.079 --> 01:27:10.359 about all this and uh oh oh, you guys look great, 1363 01:27:10.359 --> 01:27:13.039 by the way, is that I want to keep it 1364 01:27:13.079 --> 01:27:15.439 simple in the context that when we talk about companies 1365 01:27:15.439 --> 01:27:19.079 and everything, uh, you know, helping and expanding and helping 1366 01:27:19.079 --> 01:27:21.680 and expand you don't have we're not talking about anybody 1367 01:27:21.720 --> 01:27:23.880 stopping what you're doing. What you're doing is great, what 1368 01:27:24.000 --> 01:27:27.399 your cody, all you guys Janati, But but make Radfest 1369 01:27:27.439 --> 01:27:30.600 your home and the context that make it your base. Uh, 1370 01:27:30.680 --> 01:27:33.279 make it. Make it that you're telling your people, all 1371 01:27:33.319 --> 01:27:36.439 your members from the big right when Radfest ends, that 1372 01:27:36.520 --> 01:27:39.239 they need to be at Radfest, not just sitting back 1373 01:27:39.279 --> 01:27:42.000 and waiting for you know, your different meetings you have, 1374 01:27:42.079 --> 01:27:44.199 get them, get them, You're already doing that in some state. 1375 01:27:44.359 --> 01:27:45.880 But this is really what we're talking about. This is 1376 01:27:45.880 --> 01:27:48.039 the simplicity of it. This is how we're going to double. 1377 01:27:48.159 --> 01:27:50.760 This is how we're going to triple. In fact, everybody 1378 01:27:50.800 --> 01:27:53.720 here talking to your friends, your family, everybody, get into 1379 01:27:53.760 --> 01:27:56.960 this

conversation, get into this life speaking, speak it up 1380 01:27:57.199 --> 01:27:59.720 and making it that simple. Uh, you know, we're we're 1381 01:27:59.760 --> 01:28:01.960 we're come many. Thank you Joe for your presentation. All 1382 01:28:02.039 --> 01:28:04.920 you guys, like I said, you're amazing. But let's keep 1383 01:28:04.920 --> 01:28:07.720 it also to this point simple that we talked to 1384 01:28:07.800 --> 01:28:10.800 our people right when you're right, when Radfest ends, you're 1385 01:28:11.279 --> 01:28:13.520 setting them up, and you do a great job setting 1386 01:28:13.560 --> 01:28:16.199 them up now to be here and it will be 1387 01:28:16.239 --> 01:28:18.479 this then Radfest will build something that will be a 1388 01:28:18.479 --> 01:28:19.560 springboard for all of us. 1389 01:28:19.600 --> 01:28:20.800 It will build everybody. 1390 01:28:21.159 --> 01:28:24.520 That's the point. By us focusing together and this initiative, 1391 01:28:24.560 --> 01:28:27.359 we will build then everybody's initiative along with that. But 1392 01:28:27.399 --> 01:28:29.520 if we don't have that one focus, we're scattered, and 1393 01:28:29.560 --> 01:28:30.359 that's what happens. 1394 01:28:30.680 --> 01:28:38.079 Thank you, Uh one, two and three. 1395 01:28:39.600 --> 01:28:42.319 Yes, My wife is the president of our vice president 1396 01:28:42.359 --> 01:28:47.199 of ALICE, which is the Latin American Sociology Association. They 1397 01:28:47.239 --> 01:28:51.800 have their conferences every two years. So what they do 1398 01:28:51.840 --> 01:28:55.600 in the meantime is they have pre ALICE conferences all 1399 01:28:55.640 --> 01:28:58.479 over Latin America. There might be three or four or 1400 01:28:58.479 --> 01:29:02.359 five of them in Mexico alone, And optimally you want 1401 01:29:02.399 --> 01:29:05.279 those people coming to your main conference, but in truth, 1402 01:29:05.279 --> 01:29:06.680 they're not all going to go there. So what would 1403 01:29:06.720 --> 01:29:09.399 happen is you would invite just a few speakers from 1404 01:29:09.399 --> 01:29:11.920 the main conference to go to all these different locations 1405 01:29:12.199 --> 01:29:15.520 you're promoting it. My wife's the president of ten universities 1406 01:29:15.560 --> 01:29:18.720 in Mexico. We would hold one our university that would 1407 01:29:18.760 --> 01:29:21.000 give us, and we make it very an expensive for 1408 01:29:21.000 --> 01:29:23.760 the students to come. So the students, you know, pay 1409 01:29:23.800 --> 01:29:27.079 the expenses of the conference, and most of those you know, 1410 01:29:27.640 --> 01:29:30.000 ninety percent of those students and other people don't go 1411 01:29:30.039 --> 01:29:31.960 to the main conference, but you're still spreading the word. 1412 01:29:37.760 --> 01:29:42.199 Okay, so I don't even know where to start. To 1413 01:29:42.279 --> 01:29:46.640 your point, what I tell my friends, just to simplify, 1414 01:29:46.920 --> 01:29:50.800 is I'm going to the first largest conference in the 1415 01:29:50.840 --> 01:29:58.920 world on longevity. Your presentation was right on. I'm a 1416 01:29:58.960 --> 01:30:03.439 global marketing comunication expert and I'm not selling anything. I 1417 01:30:03.479 --> 01:30:06.479 want to collaborate and help. I told lis Perish that 1418 01:30:06.960 --> 01:30:11.119 I moved to Mexico because I believe that access to 1419 01:30:11.960 --> 01:30:16.880 the things that people need are much easier being in Mexico. 1420 01:30:17.279 --> 01:30:23.560 I speak Spanish, so unfortunate. So whatever is needed, I'm there. 1421 01:30:24.039 --> 01:30:25.039 I'm in Tijuana. 1422 01:30:25.319 --> 01:30:26.399 I'm right on the border. 1423 01:30:27.600 --> 01:30:31.279 One of the things that I think is critical in 1424 01:30:31.359 --> 01:30:36.560 my opinion of teaching at MBA programs, working and marketing 1425 01:30:36.560 --> 01:30:39.720 all my life is you need to think from the 1426 01:30:39.760 --> 01:30:44.119 outside and versus inside out. What does that mean when 1427 01:30:44.239 --> 01:30:48.600 I talk to people, regular people? To your point, how 1428 01:30:48.640 --> 01:30:54.159 do you double attendance? You need to get people excited 1429 01:30:54.600 --> 01:30:57.720 and passionate. The people that I talk to about this 1430 01:30:57.920 --> 01:31:03.960 concept are afraid. They're afraid, and what are they afraid of? 1431 01:31:04.800 --> 01:31:09.039 You'll never guess. They're afraid of loneliness. They're like, if 1432 01:31:09.079 --> 01:31:11.760 I outlive, I look at my mother. 1433 01:31:11.960 --> 01:31:15.600 Two of her friends just died. It's very sad. 1434 01:31:16.359 --> 01:31:20.680 So when you're talking, when you're excited, because you've already 1435 01:31:20.720 --> 01:31:24.680 bought into the concept, you cannot get through people. And 1436 01:31:24.720 --> 01:31:27.359 I'll tell you this as a marketer for many years, 1437 01:31:27.720 --> 01:31:33.279 you will just people will just be negative or they'll 1438 01:31:33.399 --> 01:31:37.399 just shut down. You will not convince them in that way. 1439 01:31:38.039 --> 01:31:41.399 So what's needed is to your point, this is a 1440 01:31:41.439 --> 01:31:44.840 time for strategy. This is a time to sit down 1441 01:31:44.960 --> 01:31:48.960 and figure out all of the strategic elements of driving 1442 01:31:49.000 --> 01:31:53.640 this movement forward. One with collaboration, one with messaging, one 1443 01:31:53.720 --> 01:31:59.119 with outreach, very clear, simple messages that can help people 1444 01:31:59.239 --> 01:32:03.199 get over the fear, look at the benefits, sell them 1445 01:32:03.279 --> 01:32:07.720 on the benefits so that you can bypass either misinformation 1446 01:32:08.800 --> 01:32:12.319 or just get them thinking in a more positive way. 1447 01:32:12.760 --> 01:32:16.359 And I'm also open to helping in any way with

that. 1448 01:32:16.359 --> 01:32:19.319 That is one of my expertises as well. But I 1449 01:32:19.399 --> 01:32:22.479 believe there's so much that can be done at this moment. 1450 01:32:22.680 --> 01:32:25.439 There's a lot of momentum, but it is a time 1451 01:32:25.479 --> 01:32:30.399 to collaborate and be strategic so that you limit the 1452 01:32:30.479 --> 01:32:36.199 resources and with less energy, you can do more and it's. 1453 01:32:36.039 --> 01:32:37.600 Hard, but it's doable. 1454 01:32:37.680 --> 01:32:42.640 You have amazing people. There's amazing people here that I'm 1455 01:32:42.720 --> 01:32:45.520 just like, I've never expected to see all of this. 1456 01:32:45.880 --> 01:32:49.239 I've been in touch with Jose, I knew about all 1457 01:32:49.279 --> 01:32:52.039 of these conferences. But there's so much more that I 1458 01:32:52.079 --> 01:32:55.000 think can be done just to move all of these forwards. 1459 01:32:55.000 --> 01:32:57.880 So again, thank you for that presentation. I think it 1460 01:32:57.920 --> 01:32:58.520 was wonderful. 1461 01:32:59.359 --> 01:33:03.399 Yeah, thank you, thank you for your comments, and we'd 1462 01:33:03.399 --> 01:33:06.319 like to connect more with you. I do want to 1463 01:33:06.399 --> 01:33:09.720 say that the more obvious opportunity is people who are 1464 01:33:09.760 --> 01:33:13.159 already into longevity. Okay, we're talking about travel, We're talking 1465 01:33:13.159 --> 01:33:15.560 about paying a registration fee, We're talking about spending a 1466 01:33:15.560 --> 01:33:19.079 couple of days somewhere. That's the obvious target. It is 1467 01:33:19.279 --> 01:33:24.119 It is the transhumanists. Okay, there's like this, there's there's 1468 01:33:24.239 --> 01:33:28.159 actually a significant number of transhumanists. There's actually a significant 1469 01:33:28.239 --> 01:33:31.119 number of longevity people. I'm not saying we shouldn't reach 1470 01:33:31.119 --> 01:33:33.039 out expand the market. We one hundred percent want to 1471 01:33:33.119 --> 01:33:36.079 do that, but let's mobilize the people who are already 1472 01:33:36.439 --> 01:33:39.600 into this to actually, you know, fucking do something. 1473 01:33:44.399 --> 01:33:45.199 I have some. 1474 01:33:45.680 --> 01:33:49.039 Feedback that might help us improve our message. There's an 1475 01:33:49.159 --> 01:33:53.520 organization called this Stage. It's an international organization of forty 1476 01:33:53.520 --> 01:33:57.439 five thousand CEOs and thirty seven countries. I'm a speaker 1477 01:33:57.479 --> 01:34:01.479 to them on sales and also longevity. My astartmental longevity 1478 01:34:01.520 --> 01:34:04.760 presentation will ask raise your hand if you would like 1479 01:34:04.840 --> 01:34:10.159 to live forever. About half raise their hand. Then I'll say, okay, 1480 01:34:10.239 --> 01:34:12.000 raise your hand if you'd like to live forever with 1481 01:34:12.039 --> 01:34:16.159 great health, a sharp mind, unhitted mobility. Now we're at 1482 01:34:16.159 --> 01:34:19.479 three quarters. And then if I ask, raise your hand 1483 01:34:19.560 --> 01:34:23.720 if you and your family and your friends could live 1484 01:34:23.760 --> 01:34:28.239 forever with great hell, almost everybody raises their hands. So 1485 01:34:28.319 --> 01:34:31.279 we might think about that and somehow it might help 1486 01:34:31.359 --> 01:34:35.560 us improve the message. The second of feedback I get 1487 01:34:35.600 --> 01:34:40.880 this negative is this is against God's will. God has 1488 01:34:40.960 --> 01:34:43.279 determined how long we're gonna live, and there's nothing we 1489 01:34:43.319 --> 01:34:46.039 can do about it. So there's no need for me 1490 01:34:46.079 --> 01:34:49.680 to get involved. I don't have an answer for that myself. Well, 1491 01:34:49.760 --> 01:34:52.279 I will tell you my wife's Catholic and that's how 1492 01:34:52.319 --> 01:34:56.760 she feels. So there's two philosophies of life determinism. So 1493 01:34:56.800 --> 01:34:59.840 I just mentioned that she believes in and the others 1494 01:35:00.079 --> 01:35:03.399 you will. That means I'm in charge of how long 1495 01:35:03.439 --> 01:35:06.920 I'm gonna live, and number one by what I do. 1496 01:35:07.039 --> 01:35:10.159 And number two, if I'm doing good for the world 1497 01:35:10.279 --> 01:35:12.880 like I think I'm trying to do, then the man 1498 01:35:12.960 --> 01:35:15.279 upstairs will see that and keep you a life longer. 1499 01:35:16.279 --> 01:35:17.880 So I just want to make sure those two main 1500 01:35:17.960 --> 01:35:20.159 pushbacks so it might help us improve our message. 1501 01:35:22.159 --> 01:35:23.279 A beautiful guess. 1502 01:35:23.159 --> 01:35:24.960 I just just a piggyback on that. 1503 01:35:25.039 --> 01:35:26.680 I do think I know I did a little bit, 1504 01:35:26.720 --> 01:35:29.000 but I do think we need to stop this like 1505 01:35:29.159 --> 01:35:34.960 boxing match with religion. Like let's let's uh yeah, yeah, 1506 01:35:35.039 --> 01:35:36.520 you know, if you believe in a god, just believe 1507 01:35:36.560 --> 01:35:37.560 in a god who wants you to live. 1508 01:35:38.680 --> 01:35:41.199 You know. Yeah, let's welcome everybody. 1509 01:35:41.560 --> 01:35:45.920 It's actually for it's actually for everybody, Yeah, because because 1510 01:35:45.960 --> 01:35:49.399 we want to live. It's not about a doctor, a doctor, 1511 01:35:49.479 --> 01:35:53.000 an agreement in doctrine. That's that's not it's not really 1512 01:35:53.000 --> 01:35:55.039 about that. It's about it's about human beings living. 1513 01:35:55.319 --> 01:35:55.520 Right. 1514 01:35:56.920 --> 01:36:03.680 Yes, So, uh, I agree with you, Joe. I think determinism, 1515 01:36:04.319 --> 01:36:08.119 irrespective of religious or philosophical roots, as a kind of 1516 01:36:08.760 --> 01:36:14.880 evolved coping mechanism that various traditions of thought have

developed 1517 01:36:14.920 --> 01:36:19.680 over the course of millennia when mortality really was unavoidable 1518 01:36:19.720 --> 01:36:23.039 because the technology just wasn't there, So people figured out 1519 01:36:23.079 --> 01:36:26.000 a way to make peace with death instead of trying 1520 01:36:26.039 --> 01:36:28.840 to fight it. The problem with that mindset is right 1521 01:36:28.880 --> 01:36:31.199 now we are on the cusp of being able to 1522 01:36:31.279 --> 01:36:34.680 kill death, but it will be dependent on our efforts. 1523 01:36:34.680 --> 01:36:40.319 So any sort of determinism or fatalism will undermine those efforts, 1524 01:36:40.399 --> 01:36:43.880 and we ultimately need the religious communities of the world 1525 01:36:43.920 --> 01:36:47.560 to align with us on this. As I've said yesterday, 1526 01:36:47.600 --> 01:36:51.479 religions evolved too, and we can hopefully influence them to 1527 01:36:51.600 --> 01:36:55.920 evolve in a positive direction without requiring people to give 1528 01:36:56.000 --> 01:36:59.279 up something that's valuable to them. So I'm an atheist, 1529 01:36:59.279 --> 01:37:01.680 but I don't want to convert anybody. If you are 1530 01:37:02.079 --> 01:37:04.279 a Christian or a Jew, or a Muslim, or a 1531 01:37:04.359 --> 01:37:06.479 Hindu or a Buddhist, I want you to be a 1532 01:37:06.560 --> 01:37:08.800 Christian or Jew, or a Muslim or Hindu or Buddhist 1533 01:37:08.800 --> 01:37:12.840 who believes in immortality or radical life extension. 1534 01:37:12.600 --> 01:37:13.319 In this world. 1535 01:37:14.560 --> 01:37:17.119 Yes, and that's that's how we can get to it together. 1536 01:37:17.159 --> 01:37:19.960 And then we could argue about theology or philosophy all 1537 01:37:19.960 --> 01:37:23.479 we want. Once we have immortality, and then we could 1538 01:37:23.479 --> 01:37:27.600 actually drill deeply into what we believe and why without 1539 01:37:27.680 --> 01:37:28.680 running out of time to do it. 1540 01:37:28.760 --> 01:37:30.479 We argue about it forever if we wanted. 1541 01:37:31.359 --> 01:37:31.439 So. 1542 01:37:31.800 --> 01:37:34.640 I don't understand the argument of it's against God's will 1543 01:37:34.680 --> 01:37:37.680 for longevity, because the Bible says we're created in God's image, 1544 01:37:37.720 --> 01:37:39.359 and I haven't heard about God dying. 1545 01:37:39.520 --> 01:37:43.239 So that's right. 1546 01:37:44.199 --> 01:37:47.199 It's the Hebrews Btseilla Melohem, right, So that's in the 1547 01:37:47.479 --> 01:37:48.960 It's in the image of God. 1548 01:37:49.319 --> 01:37:51.079 The Gospel of longevity. 1549 01:37:52.159 --> 01:37:55.439 Jim, Okay, we have a question here, Bob under balloon. 1550 01:37:56.600 --> 01:38:02.079 Yeah, I think we need to walk our I had 1551 01:38:02.119 --> 01:38:07.319 my fifty year service celebration at the Boeing Company about 1552 01:38:07.359 --> 01:38:09.640 three months ago, and it happened to be in the

1553 01:38:09.720 --> 01:38:11.680 middle of one of my fasting periods. 1554 01:38:12.039 --> 01:38:13.640 I thought, I'm not going to break my fast for this. 1555 01:38:14.079 --> 01:38:14.359 Hell. 1556 01:38:14.439 --> 01:38:19.199 No, you gotta take charge of yourself and say I'm 1557 01:38:19.199 --> 01:38:19.880 going to be different. 1558 01:38:20.159 --> 01:38:21.199 You gear are different. 1559 01:38:21.479 --> 01:38:25.439 You know, do the things and do not pay attention 1560 01:38:25.520 --> 01:38:29.279 to what the masses who follow the sheep expectation follow. 1561 01:38:29.960 --> 01:38:31.920 You're going to retire, not to death, but to do 1562 01:38:32.000 --> 01:38:38.359 more things. When you have your fifty year self fast 1563 01:38:38.359 --> 01:38:40.000 if you can fast, you know, don't stop. 1564 01:38:41.960 --> 01:38:45.920 Okay, we have time for two more questions, and also 1565 01:38:46.000 --> 01:38:48.880 remember after this we're going to have a very nice meal. 1566 01:38:49.680 --> 01:38:51.439 Life is also to be enjoyed. 1567 01:38:51.439 --> 01:38:53.920 That is why we want to be immortal, because we 1568 01:38:53.960 --> 01:38:56.920 want to have fun. We have to enjoy life, so 1569 01:38:57.560 --> 01:39:00.720 the food will be nice. But we have time for questions. 1570 01:39:00.960 --> 01:39:03.560 One question here, Taylor. 1571 01:39:04.479 --> 01:39:07.279 Yeah, I have a couple of questions. One is actually 1572 01:39:07.279 --> 01:39:12.000 for you, Jose in Madrid, are you are your speakers 1573 01:39:12.000 --> 01:39:13.880 that you have planned? Are they actually going to be 1574 01:39:13.920 --> 01:39:17.479 there in person and not over zoom because that's a 1575 01:39:17.520 --> 01:39:19.840 far away to travel for a lot of us. And 1576 01:39:19.920 --> 01:39:21.159 another is for Ganadi. 1577 01:39:21.600 --> 01:39:23.119 And we've had a lot. 1578 01:39:22.920 --> 01:39:26.000 Of exciting protocols announced here on the main stage and 1579 01:39:26.039 --> 01:39:30.359 in some of the clinics, and are you considering incorporating 1580 01:39:30.399 --> 01:39:33.920 any of those into your game, as you know things 1581 01:39:33.920 --> 01:39:36.600 that might pop up if you're advocating for anti aging. 1582 01:39:38.319 --> 01:39:41.039 Okay, the first question, yes, I like to do like 1583 01:39:41.119 --> 01:39:45.600 in Radfast, the speakers have to be there because I 1584 01:39:45.640 --> 01:39:47.640 want also the people to talk with the speakers. 1585 01:39:47.640 --> 01:39:48.439 This is important. 1586 01:39:48.720 --> 01:39:52.520 And yesterday there was a beautiful VIP reception with the 1587 01:39:52.560 --> 01:39:55.760 speakers and those participants who wanted to go, and so 1588 01:39:55.840 --> 01:39:57.000 I want them to be in touch. 1589 01:39:57.199 --> 01:39:58.560 There are certain exceptions. 1590 01:39:58.640 --> 01:40:02.359 Last year I had Brian Joe, but Brian Johnson tries 1591 01:40:02.399 --> 01:40:05.760 to avoid international trouble because of his Arcadian rhythm and 1592 01:40:05.840 --> 01:40:09.199 he's sleep and this year so he didn't come in person. 1593 01:40:09.279 --> 01:40:11.840 He was by zoom. This year I also have one 1594 01:40:11.880 --> 01:40:16.159 person byzom who is George. George Church is no longer 1595 01:40:16.199 --> 01:40:20.520 traveling internationally and so it's Ray Kersweil. He doesn't travel internationally. 1596 01:40:20.640 --> 01:40:23.600 But otherwise, all the people are coming to Madrid. Yes, 1597 01:40:23.640 --> 01:40:26.159 this is a real conference and I have tours for them. 1598 01:40:26.199 --> 01:40:29.680 I want them to enjoy life, to see how beautiful 1599 01:40:29.680 --> 01:40:33.640 life is and how fantastic the Mediterranean diet is. 1600 01:40:34.760 --> 01:40:39.319 Yes, So Taylor, to answer your question, I'm of course 1601 01:40:39.359 --> 01:40:41.920 still open to feedback on LV the game. 1602 01:40:41.920 --> 01:40:43.600 We're currently unbuild. 1603 01:40:43.479 --> 01:40:45.920 Zero point nine to one, so we're not at one 1604 01:40:45.920 --> 01:40:49.399 point zero yet. The game is open to iteration and 1605 01:40:49.640 --> 01:40:52.880 refinement now in terms of how specific do we want 1606 01:40:52.920 --> 01:40:55.960 to get. There's a reason why I had a singular 1607 01:40:56.039 --> 01:41:01.079 selection for fitness regimen and the singular selection for improve nutrition. 1608 01:41:01.199 --> 01:41:05.399 It's supposed to be whatever you think works or whatever 1609 01:41:05.520 --> 01:41:08.479 works for you or whatever ends up working in practice. 1610 01:41:08.520 --> 01:41:11.479 And the reason why I did that was because I 1611 01:41:11.520 --> 01:41:15.680 wanted to show at least the approximate scale of effects. 1612 01:41:15.760 --> 01:41:18.039 So if you engage in the. 1613 01:41:18.000 --> 01:41:21.880 Best possible fitness regimen, whatever that happens to be, that 1614 01:41:21.920 --> 01:41:25.039 could reverse your aging somewhat, that could rejuvenate you somewhat, 1615 01:41:25.079 --> 01:41:28.159 make you healthier, make you live longer. It's not going 1616 01:41:28.199 --> 01:41:30.359 to make you live to one fifty. Likewise, if you 1617 01:41:30.439 --> 01:41:33.119 have the best diet in the world, it could help 1618 01:41:33.159 --> 01:41:35.640 you live longer, it could help you avoid certain diseases. 1619 01:41:36.000 --> 01:41:38.239 It's not going to make you live to one fifty 1620 01:41:38.319 --> 01:41:42.279 or one thousand or a million years. So within the game, 1621 01:41:43.039 --> 01:41:47.640 I'm less focused on being minutely accurate. I'm more focused 1622 01:41:47.920 --> 01:41:50.479 on accuracy and relative. 1623 01:41:50.079 --> 01:41:52.560 Terms, like what is it that you would really need 1624 01:41:52.600 --> 01:41:52.880 to do? 1625 01:41:52.920 --> 01:41:57.520 What kinds of interventions to reach that

indefinite, open ended 1626 01:41:57.600 --> 01:42:02.319 lifespan immortality if you will. And that's why I not 1627 01:42:02.439 --> 01:42:05.720 only include the rejuvenation therapies. I include other causes of 1628 01:42:05.760 --> 01:42:09.920 death too, and the opportunity to fight those, which you 1629 01:42:10.000 --> 01:42:13.239 will have more time to do if you're ageless. So 1630 01:42:13.600 --> 01:42:17.760 think about all the risks facing humanity and the effect 1631 01:42:17.840 --> 01:42:19.680 size of each of them. 1632 01:42:20.479 --> 01:42:24.199 Okay, if there is one question, and also I want 1633 01:42:24.279 --> 01:42:27.960 death to ask a question. Death, come here, I want 1634 01:42:28.000 --> 01:42:30.960 you to ask a question to our panelies. So think 1635 01:42:30.960 --> 01:42:33.199 about that question. Well we have a quick one, right, 1636 01:42:33.319 --> 01:42:35.840 quick one, and then death think about it because it 1637 01:42:35.960 --> 01:42:38.359 is a matter of life or death. 1638 01:42:41.000 --> 01:42:43.560 He said, we don't want to boxing match with the religion, 1639 01:42:43.600 --> 01:42:45.760 but what if that religion wants to fight us, and 1640 01:42:45.840 --> 01:42:51.560 particularly they if they like they oppose cryonics for example. 1641 01:42:52.680 --> 01:42:58.159 Yes, what if those who are religious or of certain 1642 01:42:58.199 --> 01:42:59.840 religious persuasions want to fight us? 1643 01:43:00.039 --> 01:43:01.960 That's the question, Joe, go ahead, and I have some 1644 01:43:02.000 --> 01:43:02.560 thoughts to it. 1645 01:43:04.399 --> 01:43:07.119 Yeah, it's still it's still not a good strategy. Okay, 1646 01:43:07.319 --> 01:43:09.439 we you know, there's there's a lot of people who 1647 01:43:10.640 --> 01:43:12.199 it's just not the way we want to go. There's 1648 01:43:12.479 --> 01:43:14.159 there's a lot of people like in the middle ground 1649 01:43:14.239 --> 01:43:16.760 that we just want to bring around to our our 1650 01:43:18.279 --> 01:43:21.319 to understand what we're doing. And that's what we need 1651 01:43:21.359 --> 01:43:24.239 to keep going with. And yeah, yes, it's still the 1652 01:43:24.279 --> 01:43:26.960 best way to go. And my view is fight the dogmatism. 1653 01:43:27.159 --> 01:43:31.720 Don't fight the core of their faith or their religious tradition, 1654 01:43:32.239 --> 01:43:35.000 but fight against the fact that they want to impose 1655 01:43:35.079 --> 01:43:39.039 their views on others. And I have a rather strong 1656 01:43:39.399 --> 01:43:41.680 libertarian strict small L, not capital L. 1657 01:43:41.920 --> 01:43:44.119 But I believe in individual freedom. 1658 01:43:44.199 --> 01:43:46.479 I believe in your right to make the choices that 1659 01:43:46.560 --> 01:43:49.279 you want to make for your life and your well 1660 01:43:49.319 --> 01:43:53.680 being as a patient, as a health and wellness enthusiast, 1661 01:43:53.720 --> 01:43:57.720 as a cryonicist. So the argument from individual rights will 1662 01:43:57.760 --> 01:44:02.000 resonate with a lot of both secular and religious individuals. 1663 01:44:02.159 --> 01:44:05.479 And you can appeal to a lot of people who 1664 01:44:05.600 --> 01:44:08.640 might even be say, fundamentalists, but tell them, well, what 1665 01:44:08.720 --> 01:44:10.119 about the US Constitution? 1666 01:44:10.199 --> 01:44:11.279 What about the Bill of Rights? 1667 01:44:11.279 --> 01:44:14.600 What about what the founders wanted individuals. 1668 01:44:14.119 --> 01:44:15.640 To enjoy us their freedom? 1669 01:44:16.000 --> 01:44:20.640 Okay, now I want to say something to okay quickly. Also, 1670 01:44:20.840 --> 01:44:22.560 you got to look at the silver lining of people 1671 01:44:22.680 --> 01:44:27.199 fighting us, because that's actually progress because first things are ridiculed, 1672 01:44:27.439 --> 01:44:30.840 then they're violently opposed, and then is widely accepted as truth. 1673 01:44:31.239 --> 01:44:33.439 So we're making progress when they're fighting us. 1674 01:44:34.159 --> 01:44:36.960 Yeah, very good. Sir Arthur S. 1675 01:44:37.079 --> 01:44:41.399 Clark who said that anyway, death has the final question, 1676 01:44:42.000 --> 01:44:44.840 so it must be an immortal question. 1677 01:44:45.720 --> 01:44:48.399 I realize I strike a lot of your hearts with 1678 01:44:48.560 --> 01:44:53.439 anxiety and fear. How death do you want to ameliorate that. 1679 01:44:58.760 --> 01:44:59.640 I didn't understand it? 1680 01:45:00.000 --> 01:45:02.920 Well, I don't know if I want to alleviate the 1681 01:45:03.000 --> 01:45:06.479 fear of death as long as you exist, because fear 1682 01:45:06.880 --> 01:45:10.640 can be a powerful motivator. Now, I've been asked this 1683 01:45:10.760 --> 01:45:13.399 question a lot since I published Death Is Wrong. 1684 01:45:13.479 --> 01:45:16.760 Well, aren't you doing all this just because you're afraid 1685 01:45:17.119 --> 01:45:17.600 to die? 1686 01:45:18.239 --> 01:45:20.560 I don't deny that I'm afraid to die, but I 1687 01:45:20.680 --> 01:45:23.640 have to go deeper than that, and I have to ask, well, 1688 01:45:23.640 --> 01:45:27.039 if I'm afraid of something, why is it that I'm afraid? 1689 01:45:27.600 --> 01:45:31.600 What is it that I'm afraid to do or become? 1690 01:45:32.199 --> 01:45:35.600 I'm afraid to lose something good. I'm afraid to lose 1691 01:45:35.800 --> 01:45:39.199 life because life is good. Why am I afraid to 1692 01:45:39.199 --> 01:45:39.720 lose life? 1693 01:45:39.760 --> 01:45:40.800 Because I love life? 1694 01:45:40.880 --> 01:45:43.640 So I think fear of death isn't something to be 1695 01:45:43.960 --> 01:45:47.600 ashamed of. Fear of death stems from love of life, 1696 01:45:47.640 --> 01:45:50.039 and love of life is something that should be embraced. 1697 01:45:50.239 --> 01:45:50.680 Well. 1698 01:45:50.600 --> 01:45:57.920 As people, we need adapt to adapt to some kind 1699 01:45:57.960 --> 01:46:00.520 of catalyst in life, and we've really don't. 1700 01:46:00.600 --> 01:46:03.439 And so I would say, let's not make death the 1701 01:46:03.439 --> 01:46:06.800 catalyst of our movement. Uh, you know, I I think 1702 01:46:06.840 --> 01:46:09.479 that what Jim was talking about on the main stage. 1703 01:46:09.479 --> 01:46:12.079 I think it was Opening Night about about being. 1704 01:46:11.920 --> 01:46:17.039 Drawn to to because to consider ourselves pre human, about 1705 01:46:17.039 --> 01:46:20.600 being drawn to what will be our true human state, 1706 01:46:20.680 --> 01:46:24.479 which is which is what would be considered heaven on Earth. 1707 01:46:24.479 --> 01:46:26.760 But it's really it's really what Earth should be. 1708 01:46:27.199 --> 01:46:31.199 Ha ha yeah yeah, yeah yeah. Don't don't take it, 1709 01:46:31.319 --> 01:46:33.199 don't take it wrong. But uh. 1710 01:46:35.239 --> 01:46:37.800 I read the folks enjoy abundance. 1711 01:46:37.279 --> 01:46:40.720 And beautiful, beautiful Jim. 1712 01:46:40.800 --> 01:46:44.000 Actually, when people say that what gives meaning to life 1713 01:46:44.199 --> 01:46:47.600 is death, that is so stupid. It's like saying, what 1714 01:46:47.760 --> 01:46:52.800 gives meaning to marriage is divorce. No, what gives meaning 1715 01:46:52.880 --> 01:46:56.399 to marriage is marriage. What gives meaning to life is 1716 01:46:56.560 --> 01:47:01.039 life more life. So we are going, fine, we are 1717 01:47:01.079 --> 01:47:04.920 going to lunch. We are go and take some pictures 1718 01:47:05.359 --> 01:47:07.960 because this is for immortality and he's a very good 1719 01:47:07.960 --> 01:47:08.640 look in death. 1720 01:47:09.560 --> 01:47:11.159 So have some pictures with death. 1721 01:47:11.640 --> 01:50:20.479 Also, Happy lunch, Sa