1 00:00:00,000 --> 00:00:08,240 We're here with our next talk. Our next speaker is a science director at IndieBio, the world's 2 00:00:08,240 --> 00:00:15,580 largest biotech accelerator. She has a PhD in chemical biology and is passionate about using 3 00:00:15,580 --> 00:00:22,660 the intersection of biology, tech, and design to increasing human health spend. Now here to 4 00:00:22,660 --> 00:00:27,980 present her talk on the brave new world of bioentrepreneurship, ladies and gentlemen, June 5 00:00:27,980 --> 00:00:37,380 Aksa. Thank you so much and thank you for the organizers for having me. So I'm going to talk 6 00:00:37,380 --> 00:00:42,780 about bioentrepreneurship. And of course, when we think of entrepreneurship today, a lot of times 7 00:00:42,780 --> 00:00:48,440 we think of our Facebooks and Googles and Ubers. And we think of tech entrepreneurship. And we 8 00:00:48,440 --> 00:00:54,300 haven't seen a lot of biology startups coming out of kind of garage labs yet. And a lot of that, 9 00:00:54,400 --> 00:00:57,900 there's a bunch of reasons for that. But let's take a look a little bit, step back, 10 00:00:57,980 --> 00:01:04,540 and take a look. Even in the tech sector in the last couple of years, or decades, we've seen 11 00:01:04,540 --> 00:01:09,320 that it actually came out of academia with ARPA and a conglomerate of different academic labs. 12 00:01:09,680 --> 00:01:14,660 And the first companies that came out were actually corporations. A lot of these companies 13 00:01:14,660 --> 00:01:20,740 were infrastructural companies, you know, your IBMs, your CISCOs that built up the hardware and 14 00:01:20,740 --> 00:01:27,320 the communication pipeline for that. And then of course, we started entering kind of the hacker 15 00:01:27,320 --> 00:01:32,540 space where code has started to become open source. The technology is becoming cheaper and cheaper. 16 00:01:33,060 --> 00:01:39,100 And that really drove people to start companies. You have your, you know, kids in a garage who are 17 00:01:39,100 --> 00:01:46,360 now coding and the software and hardware is so cheap that they can start making and testing their 18 00:01:46,360 --> 00:01:53,060 ideas. And we actually do see this similar route in biotech entrepreneurship. Although even 19 00:01:53,060 --> 00:01:57,300 today, the majority of what we see is heavily in academia. And so, you know, we're seeing a lot of 20 00:01:57,320 --> 00:02:02,540 academia still. And of course, we know all our big corporations, your big pharma companies, your 21 00:02:02,540 --> 00:02:09,500 Genentechs, your Pfizers, those have been traditionally what we think of biotech. And those 22 00:02:09,500 --> 00:02:15,680 usually come out of academic labs with lots and lots of money and lots of VC backing in order to 23 00:02:15,680 --> 00:02:20,820 even get started because biotechnology is so expensive. But as we know, in the last couple of 24 00:02:20,820 --> 00:02:27,300 years, we also started seeing biohackers. So we have community labs like BioCurious, CounterCars, 25 00:02:27,320 --> 00:02:34,160 Culture Labs. And of course, you know, the interest of biohacking is increasing. And people are 26 00:02:34,160 --> 00:02:39,020 starting to think about how do we open source a lot of the methods that we've learned? How do we 27 00:02:39,020 --> 00:02:46,280 make equipment cheaper? How do we find reagents and things cheaper as well? And that really kind 28 00:02:46,280 --> 00:02:51,580 of leveraged, leveraging on that, we've started seeing entrepreneurship happening in 29 00:02:51,580 --> 00:02:55,320 biotechnology, which is really exciting. And we're still in very, very early days. 30 00:02:56,560 --> 00:03:01,300 However, there are some differences between biotech startup entrepreneurship and tech 31 00:03:01,300 --> 00:03:08,040 entrepreneurship, is that in tech, we had the microchip, which with this one chip, we were able 32 00:03:08,040 --> 00:03:13,940 to read, write code, we're able to copy, cut, paste, do all these different functions on this 33 00:03:13,940 --> 00:03:18,800 one chip. And this chip, of course, with Moore's Law over time has gone ridiculous, ridiculously 34 00:03:18,800 --> 00:03:25,100 cheap now that everyone has one in their, in their pockets. And that has not been the case for 35 00:03:25,100 --> 00:03:33,100 biotech. Biotech, each little bit of function took many, many years to put together. So in, you 36 00:03:33,100 --> 00:03:40,660 know, 1950s, we started to even figure out how to visualize DNA on a gel. And then 1967, we learned 37 00:03:40,660 --> 00:03:46,140 how we can glue two pieces of DNA together. And then how do we cut? And then how do we start 38 00:03:46,140 --> 00:03:52,840 reading? So it took over 50 years to get to where we are now, where now we only just started with 39 00:03:52,840 --> 00:03:55,080 that basic set of instructions. And that's what we're doing now. And that's what we're doing now. 40 00:03:55,100 --> 00:03:59,260 So we're building on the instructions that we could have done, that a microchip could do. And 41 00:03:59,260 --> 00:04:03,340 this is definitely on the DNA level. And from the DNA level, we can start building on new 42 00:04:03,340 --> 00:04:10,500 functionalities and technologies. So the beauty of now is that we can start thinking of biology as a 43 00:04:10,500 --> 00:04:16,180 technology, right? A lot of people have talked about using DNA, it's similar to code, and mixing 44 00:04:16,180 --> 00:04:21,240 and matching that so that we can actually build technologies out of biology. And instead of just 45 00:04:21,240 --> 00:04:25,080 thinking about medical devices and therapeutics, biology can actually be used to do things like 46 00:04:25,100 --> 00:04:29,180 that. And that can be a technology for all different sectors of society, such as food and 47 00:04:29,180 --> 00:04:37,880 agriculture is a big one, consumer biotech, neurotech, bio data, industrial tech, and then of 48 00:04:37,880 --> 00:04:44,780 course, our medical devices and biopharma. And the interesting thing is that there's so many more 49 00:04:44,780 --> 00:04:50,080 applications yet to be discovered, and we're really excited to learn about what those could be. 50 00:04:51,840 --> 00:04:55,080 So there's some driving forces that cause biotech to be a technology, and biotech to be a 51 00:04:55,080 --> 00:05:02,620 biotechnology entrepreneurship to actually start in these last few decades, or in the last few 52 00:05:02,620 --> 00:05:09,440 years. One of the forces is actually called the post-docalypse, if you've heard of this. This is 53 00:05:09,440 --> 00:05:15,580 where basically there's not enough professorship positions, and the grant money is very limited, 54 00:05:15,760 --> 00:05:22,200 that PhDs who are well-trained end up going for post-doc after post-doc after post-doc, and there 55 00:05:22,200 --> 00:05:23,380 seems to be no end to that. 56 00:05:25,080 --> 00:05:30,540 This gives us a huge amount of talented people who don't know what to do with themselves, and so it 57 00:05:30,540 --> 00:05:37,040 would be great if we can redirect their efforts into starting their own companies. There's faster 58 00:05:37,040 --> 00:05:41,600 science being done. Of course, with Moore's Law and all the technological innovations, we now have 59 00:05:41,600 --> 00:05:49,840 bioinformatics. We can sequence DNA, write DNA much, much faster. And then coupled with that is 60 00:05:49,840 --> 00:05:55,060 experiments are becoming cheaper. Equipment is becoming cheaper, reality is becoming cheaper, 61 00:05:55,080 --> 00:05:58,340 biosecurity is becoming cheaper, the agents are more accessible. There are contract research 62 00:05:58,340 --> 00:06:04,320 organizations that you can send out your work, such as Cloud Labs that you can do your work on. So 63 00:06:04,320 --> 00:06:11,340 that all really ‑‑ all of these three factors is really driving why right now is a great 64 00:06:11,340 --> 00:06:14,220 opportunity to start a biotech company. 65 00:06:15,620 --> 00:06:22,400 And so, that was the thesis on which IndieBio was founded on. We had a hypothesis about two and a 66 00:06:22,400 --> 00:06:25,060 half years ago to build a accelerated biotech innovation, and the one that we found was the best 67 00:06:25,080 --> 00:06:29,980 program to help train scientists into entrepreneurs and teach them about how 68 00:06:29,980 --> 00:06:37,180 to start companies and so that's what the basis of what we do and we have four 69 00:06:37,180 --> 00:06:42,560 we do a four month startup accelerator program it comes with 250k in funding 70 00:06:42,560 --> 00:06:48,300 which we take equity in and we have a fully equipped biotech lab and 71 00:06:48,300 --> 00:06:52,660 this is one of the most important parts because in biotech if you don't have a 72 00:06:52,660 --> 00:06:56,380 lab oftentimes you don't have the resources to start your company so then 73 00:06:56,380 --> 00:06:59,700 it becomes a chicken-and-egg thing because everyone request wants you to 74 00:06:59,700 --> 00:07:02,920 have a prototype but you can't build your prototype until you have some money 75 00:07:02,920 --> 00:07:08,160 to start your lab so this really helps by using a shared lab to have these 76 00:07:08,160 --> 00:07:14,000 companies work through and develop their their initial prototypes our program 77 00:07:14,000 --> 00:07:18,120 also has over 200 mentors and we're located in downtown San Francisco so at 78 00:07:18,120 --> 00:07:22,440 the heart of Silicon Valley and that is you know following a lot of the 79 00:07:22,440 --> 00:07:22,640 research that's going on in Silicon Valley and that is you know following a lot of the 80 00:07:22,660 --> 00:07:22,740 research that's going on in Silicon Valley and that is you know following a lot of the 81 00:07:22,740 --> 00:07:27,420 the tech entrepreneurs and the tech VCS were kind of redirecting a lot of those 82 00:07:27,420 --> 00:07:34,040 efforts into into biotech so I mentioned kind of the different segments that we've 83 00:07:34,040 --> 00:07:38,020 invested in and that we're very excited about I'm gonna go through some of the 84 00:07:38,020 --> 00:07:43,280 companies that we've we've done in these different categories so one of the 85 00:07:43,280 --> 00:07:48,180 probably most noted one is called Memphis meats this meatball here is 86 00:07:48,180 --> 00:07:52,380 actually made from stem cells so this company has done the 87 00:07:52,380 --> 00:07:59,200 this for pork beef chicken and duck so far and so this movement is called 88 00:07:59,200 --> 00:08:03,720 cellular agriculture or clean meat because not only is it a humanitarian 89 00:08:03,720 --> 00:08:07,440 thing or animal rights thing where we're not slaughtering animals and you're 90 00:08:07,440 --> 00:08:11,180 moving away from factory farming but also it's clean because there's no 91 00:08:11,180 --> 00:08:17,120 antibiotics there's no contamination in our food so while currently it is still 92 00:08:17,120 --> 00:08:20,720 very very expensive to do this in the lab over the next few years we should 93 00:08:20,720 --> 00:08:22,360 see this being really important and I think it's going to be really important for us to do this in the lab over the next few years we should see this being 94 00:08:22,360 --> 00:08:27,400 relatively similar to what you would buy from a restaurant so that's very 95 00:08:27,400 --> 00:08:34,060 exciting for meat and potentially vegetarians another really interesting 96 00:08:34,060 --> 00:08:38,620 area in the food sector is actually breaking down foods to their molecular 97 00:08:38,620 --> 00:08:44,760 level so this company Ava wineries was started by two guys who went to Napa and 98 00:08:44,760 --> 00:08:49,060 saw a really really expensive bottle of wine and said to themselves we're never 99 00:08:49,060 --> 00:08:52,220 going to be rich enough to drink that wine and it's like but wait a second 100 00:08:52,360 --> 00:08:57,680 wine is just a bunch of molecules so why can't we recreate that wine so that's 101 00:08:57,680 --> 00:09:02,080 exactly what they do they take wines they throw it in a mass spectrometer and 102 00:09:02,080 --> 00:09:06,540 analyze the different components and their concentrations and now they're 103 00:09:06,540 --> 00:09:12,300 putting them back in their their correct compositions right so now this is like 104 00:09:12,300 --> 00:09:17,320 pennies on the dime and they can make essentially whatever varietal or 105 00:09:17,320 --> 00:09:22,280 whatever wine you would want and the fascinating thing about 106 00:09:22,280 --> 00:09:27,860 this is we're now looking at food from not just the the you know the food 107 00:09:27,860 --> 00:09:32,240 itself but we're looking at it on the molecular level and that when we change 108 00:09:32,240 --> 00:09:36,900 small the molecules we can have different properties we can you know in 109 00:09:36,900 --> 00:09:40,400 the case of wine we can eliminate sulfide so that you don't have hangovers 110 00:09:40,400 --> 00:09:46,120 as much so this has a lot of promise in the future of developing new types of 111 00:09:46,120 --> 00:09:51,920 foods that we can work with going into consumer biotech this 112 00:09:52,280 --> 00:09:58,420 leather here is made from mushrooms mycelium actually create this collagenous 113 00:09:58,420 --> 00:10:03,640 fiber and you can grow them into sheets and it's really nice because you can 114 00:10:03,640 --> 00:10:07,900 also grow patterns so you can't grow cow with with different kinds of 115 00:10:07,900 --> 00:10:12,360 patterns but you can do this with with the mushrooms this this particular 116 00:10:12,360 --> 00:10:16,340 mushroom and this that this particular company micro works that's made it feels 117 00:10:16,340 --> 00:10:21,880 amazing just like real leather and they've shown that with a full cow's 118 00:10:21,880 --> 00:10:22,140 high 119 00:10:22,280 --> 00:10:25,700 piece of leather which normally takes two years to grow because you have to 120 00:10:25,700 --> 00:10:29,080 feed the cow and the growth of the cow has to grow up they can make that in two 121 00:10:29,080 --> 00:10:33,900 weeks so think of the fraction of the cost and the environmental impact that 122 00:10:33,900 --> 00:10:40,780 that saves for having these kind of new leather products available in neuro tech 123 00:10:40,780 --> 00:10:45,160 one of the companies that's that's kind of far out there but I'm extremely 124 00:10:45,160 --> 00:10:51,240 interesting is neuro computation this company near Hanukkah has a chip where 125 00:10:51,240 --> 00:10:52,260 they embed a chip in a machine and they embed a chip in a machine and they embed 126 00:10:52,280 --> 00:10:58,200 the neurons in different formations so that the connectivity can essentially you 127 00:10:58,200 --> 00:11:03,580 can do computation on that so this company is yeah going ahead and hopefully 128 00:11:03,580 --> 00:11:10,600 in the next few years making the first brain the first bio brain computer from 129 00:11:11,300 --> 00:11:18,180 a data side this company called catalog is storing archival data digital data 130 00:11:18,180 --> 00:11:22,180 into DNA and why would you do this well for one 131 00:11:22,180 --> 00:11:26,420 DNA is actually a million times more dense than flash drives which is the 132 00:11:26,420 --> 00:11:30,940 currently most dense form of storage and of course when you're talking about 133 00:11:30,940 --> 00:11:35,680 archival you right now it's done with magnetic tapes and they're in large 134 00:11:35,680 --> 00:11:39,300 facilities that have to be cooled and actually every 20 years you'll have to 135 00:11:39,300 --> 00:11:44,120 recopy the magnetic tapes because they go bad well with DNA you if you freeze 136 00:11:44,120 --> 00:11:49,940 it and dry it down we know that we can store it for pretty much infinite 137 00:11:49,940 --> 00:11:51,920 infinitely there's actually 138 00:11:51,920 --> 00:11:59,080 a case where there was a 60,000 year old mammoth that was uncovered and they 139 00:11:59,080 --> 00:12:03,320 uncovered the DNA from that so it's very likely that we can store the DNA for a 140 00:12:03,320 --> 00:12:09,300 long long time and the lastly DNA can be copied very very easily with a well 141 00:12:09,300 --> 00:12:13,260 known technique called polymerase chain reaction so within two hours you can 142 00:12:13,260 --> 00:12:18,920 essentially copy your entire petabytes of data over so this is very exciting 143 00:12:18,920 --> 00:12:21,140 for the future of storage 144 00:12:23,320 --> 00:12:27,420 another company in the kind of a bio data space is called scaled so you can 145 00:12:27,420 --> 00:12:33,780 imagine entire laboratory work worth of work done in a micro fluidic chip and 146 00:12:33,780 --> 00:12:38,820 this chip houses 80,000 different experiments running at the same time it 147 00:12:38,820 --> 00:12:42,120 uses different combinations of molecules to test the different 148 00:12:42,120 --> 00:12:46,780 conditions and what you can use this for is for stem cell differentiation stem 149 00:12:46,780 --> 00:12:51,840 cells differentiate at a very specific condition and by using the screen this 150 00:12:51,920 --> 00:12:56,140 company has actually shown that they can make a kidney organoid so basically a 151 00:12:56,140 --> 00:13:02,120 small set of cells and actually 27 different types of cells as a kidney and 152 00:13:02,120 --> 00:13:07,200 and using this technology so this the kidney of course can then eventually be 153 00:13:07,200 --> 00:13:11,420 made potentially into full kidneys but can also be used for drug development 154 00:13:11,420 --> 00:13:17,720 drug screening etc going on to industrial biotech we have company 155 00:13:17,720 --> 00:13:21,900 called Yuba biologics which is reclaiming coal mining and 156 00:13:21,920 --> 00:13:27,300 gold mining water so the obviously the runoff from these processes is very 157 00:13:27,300 --> 00:13:31,480 toxic there's high amounts of sulfide in it and they've found a cocktail of 158 00:13:31,480 --> 00:13:39,100 microbes that can purify the water and put it back into the lake and medical 159 00:13:39,100 --> 00:13:45,960 devices this one is called Knox medical and it's a spirometer for for measuring 160 00:13:46,540 --> 00:13:51,860 your breathing for kids with asthma so the idea is the kid would blow a 161 00:13:51,860 --> 00:13:55,420 needle into this every single day and you would be able to see the changes in 162 00:13:55,420 --> 00:13:59,680 their lung capacity and this way you can actually predict when a asthma attack 163 00:13:59,680 --> 00:14:04,500 might happen days before it happens so that the parents can help medicate the 164 00:14:04,500 --> 00:14:09,360 kid and then last but not least I want to mention we have a lot of 165 00:14:09,360 --> 00:14:13,780 pharmaceutical biopharma companies a lot of them in cancer this particular one 166 00:14:13,780 --> 00:14:19,200 actually works with snake venom if you guys don't know how snake that's anti 167 00:14:19,200 --> 00:14:21,760 venoms are currently done you actually have people 168 00:14:21,860 --> 00:14:27,880 going and milking a snake and then this then they take the snake venom inject it 169 00:14:27,880 --> 00:14:32,340 into a horse and then they they lyophilize they dry up that horse serum 170 00:14:32,340 --> 00:14:37,200 so if you got bit by a snake you get rushed to the hospital you hope that 171 00:14:37,200 --> 00:14:41,180 that hospital has that venom you hope that you remember which snake bit you 172 00:14:41,180 --> 00:14:45,740 because it's very specific and then if they had this anti venom they inject 173 00:14:45,740 --> 00:14:50,800 horse serum into you so this is a very kind of archaic practice 174 00:14:51,860 --> 00:14:58,680 horse by horse there's no QC there so it can vary and and also you are 175 00:14:58,680 --> 00:15:01,500 injected with a whole bunch of horse blood so oftentimes people have 176 00:15:01,500 --> 00:15:06,180 anaphylactic shock to the horse blood itself and of course this is this is an 177 00:15:06,180 --> 00:15:08,900 area where you know kind of the developing world hasn't paid a lot of 178 00:15:08,900 --> 00:15:12,700 attention to because we don't have that many snakes and but of course in 179 00:15:12,700 --> 00:15:16,880 Southeast Asia and Africa that's it's a huge problem lots of lots of people have 180 00:15:16,880 --> 00:15:21,840 to you know cut off limbs because of the young the snake venoms starting to get in there. 181 00:15:21,860 --> 00:15:28,640 So what this company is doing is using more pharmacological advancements in the 182 00:15:28,640 --> 00:15:33,100 development of antibodies to address this issue and so one thing they did is 183 00:15:33,100 --> 00:15:36,500 they mapped out well what are all those different kinds of snakes snake venom 184 00:15:36,500 --> 00:15:43,500 antivenoms or the molecules in a region and they have a cocktail solution so 185 00:15:43,500 --> 00:15:50,100 that you have 99% coverage of a snake bite so it like 99% of different 186 00:15:50,100 --> 00:15:51,820 species will be covered in this one. 187 00:15:51,860 --> 00:15:56,820 shot and furthermore the shot instead of rushing to a hospital you can actually 188 00:15:56,820 --> 00:15:59,940 bring the shot with you so you can imagine if you were going to Southeast 189 00:15:59,940 --> 00:16:04,480 Asia you're gonna go into the jungles you can bring the shot with you and if 190 00:16:04,480 --> 00:16:08,300 you accident accidentally get bitten by a snake then you can inject yourself 191 00:16:08,300 --> 00:16:12,400 immediately and stop that the progression of that anti that 192 00:16:14,680 --> 00:16:21,840 degradation of your limbs. So so how do you get involved in bioentrepreneurship 193 00:16:21,860 --> 00:16:26,360 if you're thinking about starting a startup in the future or you're just you know early 194 00:16:26,360 --> 00:16:31,940 and thinking and dabbling in the space some suggestions is engaging in communities. 195 00:16:32,200 --> 00:16:36,900 Obviously this biohacking village is an amazing community DEF CON is an amazing community 196 00:16:36,900 --> 00:16:41,900 there are a lot of biohacker spaces around the country and around the world now that 197 00:16:41,900 --> 00:16:47,580 you can engage in and furthermore you should engage with scientists and talk to people 198 00:16:47,580 --> 00:16:51,840 in the particular fields that you're interested in see what their pain points are see what 199 00:16:51,860 --> 00:17:00,480 what kind of novel ideas come out of that. Definitely find a co-founder. Sometimes in 200 00:17:00,480 --> 00:17:07,480 software you can get along with just being your own founder, but in biotech you definitely 201 00:17:07,480 --> 00:17:15,680 cannot because usually we advise that you have one scientific and technical lead and 202 00:17:15,680 --> 00:17:20,920 one business person. There's just way too much to do that you definitely need some co-founders 203 00:17:20,920 --> 00:17:29,520 to help you in the process. In general, with the maker ethos, tinker, make, try, I don't 204 00:17:29,520 --> 00:17:36,300 advise trying things on yourself, but do try on other experiments, other organisms first 205 00:17:36,300 --> 00:17:45,340 in an ethical manner. And then don't be afraid of failure, of course. Biology is an extra 206 00:17:45,340 --> 00:17:50,540 level of difficulty where sometimes nature doesn't allow things. So things will fail, 207 00:17:50,600 --> 00:17:50,880 definitely. 208 00:17:50,880 --> 00:17:57,480 But keep persisting. And that's why Ph.D. programs are like seven years now. So if you 209 00:17:57,480 --> 00:18:04,720 continue to progress and learn from mistakes and try and pivot, there will be ways to make 210 00:18:04,720 --> 00:18:11,560 a successful startup. And then if you are thinking about venture funding, which not all 211 00:18:11,560 --> 00:18:16,360 companies have to be venture funded, some of the things to consider is that you do need some 212 00:18:16,360 --> 00:18:20,600 kind of technical insight that gives you an unfair advantage. So often this is called the 213 00:18:20,600 --> 00:18:20,860 IPA. 214 00:18:20,880 --> 00:18:26,580 Often times you don't have to start off with an IP in order to apply for venture funding, but you 215 00:18:26,580 --> 00:18:32,840 have to at least have a road map to how you would gain IP. How do you make that insight and that IP 216 00:18:32,840 --> 00:18:38,280 into a product? Obviously science by itself is not a product. So you have to figure out what the 217 00:18:38,280 --> 00:18:43,040 product is, who's going to use it, who would actually buy it. And then furthermore, how do you 218 00:18:43,040 --> 00:18:47,720 turn that product into a sustainable business, whether that be you're selling a razor blade model 219 00:18:47,720 --> 00:18:50,860 or you have one product that follows with multiple products. So you have to figure out how to 220 00:18:50,860 --> 00:18:56,500 use multiple other products later. So figuring out that dynamic and how you would grow your 221 00:18:56,500 --> 00:19:02,200 business. And then lastly, with venture capital, we always think of how it has to have a big 222 00:19:02,200 --> 00:19:07,520 impact on the world. So how would your business potentially touch a billion people in the world? 223 00:19:08,020 --> 00:19:14,440 And that's ultimately what we really want to do is we think that biotechnology is so impactful. 224 00:19:14,660 --> 00:19:19,380 It is one of the technologies that can scale relatively easily because it is grown. 225 00:19:20,860 --> 00:19:25,920 And so we want to make an impact in the world. So if you have any questions, I can take them now. 226 00:19:26,020 --> 00:19:30,900 But you should check out our website. And I'm happy to answer any questions. 227 00:19:33,860 --> 00:19:34,660 Thank you. 228 00:19:34,660 --> 00:19:38,560 Thank you very much.