WEBVTT - Many New mRNA Applications (Audio) 0:00:04.480 --> 0:00:08.480 This is Bloomberg Business Week with Carol Masser and Bloomberg 0:00:08.560 --> 0:00:13.920 Quick Takes Tim Stenovik from Bloomberg Radio. I'm Carol Masser 0:00:14.040 --> 0:00:16.600 and I'm Tim Stanovik, the cover story this week. At 0:00:16.600 --> 0:00:18.320 the beginning of the pandemic, a few of us had 0:00:18.400 --> 0:00:21.200 ever heard of Moderna. Now the company is a household 0:00:21.280 --> 0:00:24.360 name with a billion dollar market cap, and it's COVID 0:00:24.480 --> 0:00:27.840 nineteen vaccine may have nineteen billion dollars in sales this year. 0:00:28.200 --> 0:00:31.080 So what comes next? The company has or will soon 0:00:31.160 --> 0:00:34.280 have messenger RNA based vaccines and trials for no fewer 0:00:34.320 --> 0:00:39.120 than ten different viruses, including flu, HIV, and zika, And 0:00:39.159 --> 0:00:42.160 if that's not enough, it's also working on cancer, rare 0:00:42.200 --> 0:00:45.920 genetic diseases, and even heart disease. The company's CEO sees 0:00:46.040 --> 0:00:49.160 m RNA coming to dominate the market for viral vaccines 0:00:49.200 --> 0:00:51.960 and one day make the hard work of designing drugs 0:00:51.960 --> 0:00:55.560 and vaccines a bit easier, more like creating software. If 0:00:55.560 --> 0:00:58.240 he can pull it off, the medical implications would be huge, 0:00:58.520 --> 0:01:01.160 as with the financial payoff for the company, But it's 0:01:01.160 --> 0:01:03.920 not going to be easy for Maderna now that Messenger 0:01:04.040 --> 0:01:08.720 RNA vaccines have succeeded so spectacularly, every major vaccine company 0:01:08.760 --> 0:01:11.160 is trying to catch up, and as it expands beyond 0:01:11.200 --> 0:01:14.360 COVID Maderna will have to prove messenger RNA can work 0:01:14.360 --> 0:01:18.000 in large trials for difficult to treat diseases such as cancer. 0:01:18.560 --> 0:01:22.120 A year ago, Moderna was an unprofitable company with no 0:01:22.280 --> 0:01:27.440 marketed products and a promising but totally unproven technology. None 0:01:27.480 --> 0:01:30.600 of its experimental drugs and vaccines had ever completed a 0:01:30.720 --> 0:01:34.640 large scale trial. Experts were divided on how well the 0:01:34.760 --> 0:01:38.000 mRNA based COVID nineteen vaccine it was about to enter 0:01:38.040 --> 0:01:41.520 in a phase three trial with stack up against older, 0:01:41.640 --> 0:01:46.679 more established vaccine technologies. This year, Moderna could deliver one 0:01:46.840 --> 0:01:50.640 billion doses of its COVID shot and bring in nineteen 0:01:50.680 --> 0:01:55.080 billion dollars in revenue. It's become the rare biotech to 0:01:55.160 --> 0:01:58.000 hit the big time without being gobbled up by or 0:01:58.160 --> 0:02:03.440 splitting profits with larger, more established company. It's worth over 0:02:03.600 --> 0:02:07.840 ninety billion dollars more than stalwarts such as Bayer, the 0:02:07.920 --> 0:02:12.160 German inventor of aspirin, and biotech peers such as Biogen 0:02:12.440 --> 0:02:16.760 founded three decades prior. The speed at which Moderna and 0:02:16.840 --> 0:02:20.799 its primary mRNA competitor, a partnership between Fiser and bi 0:02:20.880 --> 0:02:24.720 on Tech, devised their shots, has made a major contribution 0:02:24.800 --> 0:02:28.440 to the fight to end the pandemic. With strong efficacy, 0:02:28.600 --> 0:02:33.120 steady supply, and no show stopping safety scares, officials are 0:02:33.120 --> 0:02:37.520 carefully monitoring rare heart inflammation cases in teenagers and young adults. 0:02:37.919 --> 0:02:41.600 mRNA shots have become the vaccines of choice, at least 0:02:41.639 --> 0:02:45.080 in countries that can get them. But for Moderna Chief 0:02:45.120 --> 0:02:50.160 executive officer Stefan Bonsel, the COVID vaccine is just the beginning. 0:02:50.720 --> 0:02:54.720 He's long promised that if mRNA works, it'll lead to 0:02:54.760 --> 0:02:58.519 a giant new industry capable of treating most everything from 0:02:58.560 --> 0:03:03.040 heart disease to cancer to rare genetic conditions. Moderna has 0:03:03.120 --> 0:03:06.200 drugs and trials for all three of these categories, and 0:03:06.280 --> 0:03:09.239 bon Cell says his company can also become a dominant 0:03:09.320 --> 0:03:13.640 vaccine maker, developing shots for emerging viruses such as NIPA 0:03:13.720 --> 0:03:16.840 and zica, as well as better known, hard to target 0:03:16.880 --> 0:03:20.959 pathogens such as HIV. In the past forty years, more 0:03:21.000 --> 0:03:25.360 than fifty new human viruses have been discovered, only three 0:03:25.400 --> 0:03:30.359 have authorized vaccines. Bonzell views that as an opportunity We're 0:03:30.360 --> 0:03:33.639 going to totally disrupt the vaccine market, he says, during 0:03:33.680 --> 0:03:38.000 a late May interview at modernist Cambridge, Massachusetts headquarters, which 0:03:38.080 --> 0:03:40.640 fills a ten story building north of the m I 0:03:40.720 --> 0:03:44.680 T campus. The Swiss drug maker Novartists occupies labs in 0:03:44.720 --> 0:03:48.520 an adjacent building, and Fighter and Merk have offices a 0:03:48.560 --> 0:03:53.000 few blocks away. Bonzell, who's forty eight, wears a pressed 0:03:53.000 --> 0:03:56.280 blue shirt, dark blue jeans, and a black air miss belt. 0:03:56.800 --> 0:04:00.200 An avid runner, he appears even trimmier in person than 0:04:00.240 --> 0:04:05.000 on his frequent virtual conference appearances. He repeatedly jumps to 0:04:05.080 --> 0:04:07.920 his feet during the interview to graph on a whiteboard 0:04:07.960 --> 0:04:12.680 how the COVID outbreak could evolve. One chart forecast seasonal 0:04:12.680 --> 0:04:18.320 waves declining each passing year, but still significant. Another projects 0:04:18.360 --> 0:04:22.080 the possible decay of vaccine efficacy over time, with m 0:04:22.200 --> 0:04:26.240 RNA shots like his starting in the best position but 0:04:26.360 --> 0:04:31.000 gradually declining. Countries may want to stockpile booster shots soon. 0:04:31.880 --> 0:04:35.239 My mother is seventy two and she has leukemia, he says, 0:04:36.080 --> 0:04:38.400 I don't want her to go through the fall without 0:04:38.400 --> 0:04:42.520 a boost. The company has vaccines for ten viruses that 0:04:42.560 --> 0:04:46.279 are in or about to be in human trials. These 0:04:46.320 --> 0:04:49.320 include three types of COVID nineteen boosters that are in 0:04:49.400 --> 0:04:52.920 mid stage trials, a seasonal flu shot that began its 0:04:52.960 --> 0:04:56.760 first human study in July, and HIV shots that are 0:04:56.760 --> 0:05:01.360 slated to begin studies later this year. The furthest along 0:05:01.480 --> 0:05:06.359 besides the covid shots, combat cit omegalovirus, a ubiquitous bug 0:05:06.440 --> 0:05:09.800 that spreads through bodily fluids and is a common cause 0:05:09.839 --> 0:05:13.080 of birth defects. It's set to begin a Phase three 0:05:13.120 --> 0:05:16.720 trial this year in women of childbearing age. In the 0:05:16.800 --> 0:05:20.640 long term, Moderna is aiming to develop an annual supershot 0:05:20.720 --> 0:05:25.920 that could suppress numerous respiratory ailments, including covid, the flu, 0:05:26.200 --> 0:05:29.520 and others. Our goal is to give you several m 0:05:29.640 --> 0:05:33.080 RNA's in a single shot at your local CVS or 0:05:33.160 --> 0:05:38.679 GP every August or September. Bond Sell says now comes 0:05:38.720 --> 0:05:42.479 the difficult part delivering on that promise while keeping ahead 0:05:42.480 --> 0:05:45.200 of just about every other vaccine company in the world 0:05:45.560 --> 0:05:49.360 as they rapidly invest in m RNA. In the future, 0:05:49.440 --> 0:05:52.600 MODERNA won't have the pandemic to highlight m r as 0:05:52.720 --> 0:05:58.880 most obvious advantages over older technologies, speed and flexibility. Future 0:05:58.960 --> 0:06:01.680 vaccines and drug will usually have to go through the 0:06:01.800 --> 0:06:06.480 US Food and Drug Administration's normal approval process, meaning longer 0:06:06.520 --> 0:06:09.360 follow ups to gather data and six to ten month 0:06:09.440 --> 0:06:13.920 review timelines. That time frame will provide space for mRNA 0:06:14.040 --> 0:06:18.200 wielding rivals and older technologies to compete. Fiser, with its 0:06:18.200 --> 0:06:21.839 partner by On Tech, has become an m RNA manufacturing 0:06:21.920 --> 0:06:26.000 juggernaut and expects to produce three billion doses this year. 0:06:26.520 --> 0:06:30.120 It has also dominated foreign distribution of m RNA vaccine 0:06:30.200 --> 0:06:35.360 so far. Another vaccine from Kervak in Germany, which took 0:06:35.360 --> 0:06:39.600 a different approach to m RNA, performed tepidly, proving only 0:06:39.760 --> 0:06:43.279 forty eight percent effective in phase three trial data released 0:06:43.320 --> 0:06:48.120 in June, but still another from China's While vax Biotechnology 0:06:48.160 --> 0:06:52.280 will soon begin phase three testing in seven countries, more 0:06:52.400 --> 0:06:57.760 established technologies are reasserting themselves too. On June fourteenth, Novovac 0:06:57.920 --> 0:07:03.000 said it's recombinant protein vaccine was effective in a nearly 0:07:03.120 --> 0:07:06.920 thirty thousand person trial in the US and Mexico with 0:07:07.040 --> 0:07:11.080 relatively few side effects, results that more or less matched 0:07:11.160 --> 0:07:15.680 those of the best mRNA shots vaccine. Giant Sinophi and 0:07:15.760 --> 0:07:19.080 Glaxow Smith Klein are in Phase three trials of their 0:07:19.120 --> 0:07:22.520 own protein based COVID vaccine, which could hit the market 0:07:22.560 --> 0:07:26.680 by year end. Many for Uhar, an analyst at s 0:07:26.760 --> 0:07:32.520 vp Lerinc, Calls Moderna's accomplishments with the COVID vaccine truly breathtaking, 0:07:33.040 --> 0:07:36.200 but he also says it's far from certain whether such 0:07:36.280 --> 0:07:40.720 vaccines will have clear efficacy advantages with other viral diseases, 0:07:41.400 --> 0:07:43.960 and how big a role of the technology could play 0:07:43.960 --> 0:07:48.040 in treating non infectious diseases such as cancer is unknown, 0:07:48.840 --> 0:07:52.960 So though public expectations are boundless, he says, the revenue 0:07:52.960 --> 0:07:57.600 opportunity is not the reply for Boncell and the others 0:07:57.640 --> 0:08:02.240 pouring money into tiny RNA strands lies in those two 0:08:02.320 --> 0:08:06.760 key advantages of speed and adaptability. At their heart, mRNA 0:08:06.880 --> 0:08:10.880 vaccines are modular technology. They deliver the genetic code telling 0:08:10.960 --> 0:08:14.160 cells how to make the virus proteins that provoke an 0:08:14.200 --> 0:08:17.400 immune response, and the cells do the hard work from there. 0:08:18.320 --> 0:08:21.480 Now that Moderna is profitable and sitting on almost eight 0:08:21.520 --> 0:08:25.880 billion dollars in cash, bon Sell's own stake including options, 0:08:26.240 --> 0:08:29.520 is worth around seven billion dollars according to the Bloomberg 0:08:29.600 --> 0:08:33.920 Billionaires Index, it can move quickly and aggressively into numerous 0:08:34.040 --> 0:08:37.720 new applications simply by changing the genetic code it puts 0:08:38.040 --> 0:08:42.440 into the m RNA. While modernas shot appears to be 0:08:42.520 --> 0:08:46.360 holding up well against the currently surging delta variant, for example, 0:08:46.840 --> 0:08:50.679 it's a straightforward process for the company to incorporate mutations 0:08:50.720 --> 0:08:54.040 into the vaccine if needed. We don't have to introduce 0:08:54.080 --> 0:08:58.479 new technology or new processes. Bon Sell says. It's exactly 0:08:58.520 --> 0:09:01.800 the same thing when Bontell left the top job at 0:09:01.800 --> 0:09:05.520 the French diagnostics company Bio Murio and became the second 0:09:05.559 --> 0:09:08.600 employee at Moderna. The name is a mashup of modified 0:09:08.679 --> 0:09:13.240 and RNA. A decade ago, the idea that messenger RNA 0:09:13.440 --> 0:09:17.480 could be medically useful was radical at the time. The molecule, 0:09:17.520 --> 0:09:21.040 which evolved to carry protein blueprints from DNA in the 0:09:21.120 --> 0:09:25.280 cells nucleus to the compartments that synthesized proteins, had a 0:09:25.320 --> 0:09:29.720 reputation among lab scientists as fragile and hard to work with. 0:09:30.280 --> 0:09:33.600 When m RNA is artificially inserted in the human body, 0:09:33.960 --> 0:09:36.800 the immune system identifies it as a threat and a 0:09:36.920 --> 0:09:41.640 tax it, and because m RNA's function is temporary, enzymes 0:09:41.640 --> 0:09:44.559 found throughout the body can break it down. Neither a 0:09:44.640 --> 0:09:48.760 desirable outcomes for a drug or vaccine. Starting in two 0:09:48.800 --> 0:09:53.719 thousand five, two researchers at the University of Pennsylvania Catalincaiko 0:09:53.880 --> 0:09:57.840 and Drew Wisseman managed to slightly modify mRNA so it 0:09:57.920 --> 0:10:00.760 generated less of an immune reaction and in the body. 0:10:01.320 --> 0:10:04.520 The finding drew little recognition at the time, but it 0:10:04.600 --> 0:10:08.240 turned out to be a critical advance. Catalan left Pen 0:10:08.360 --> 0:10:13.360 to join BioNTech in in a trio of Harvard at 0:10:13.480 --> 0:10:17.520 m I T scientists founded by venture firm Flagship Pioneering 0:10:17.800 --> 0:10:21.360 picked up on the idea and founded Moderna, bringing Boncell 0:10:21.480 --> 0:10:25.520 on the next year. Moderna and BioNTech later licensed the 0:10:25.600 --> 0:10:30.520 PEN technology. Boncell recalls telling his wife before he changed jobs, 0:10:30.559 --> 0:10:33.080 that there was a five percent chance the m RNA 0:10:33.240 --> 0:10:37.800 concept would succeed, but if it did, it would be huge. 0:10:38.040 --> 0:10:41.560 When Boncell pitched Moderna's now president, Stephen Hog on the 0:10:41.600 --> 0:10:45.600 company the following year, Hoax says his reaction was he's 0:10:45.600 --> 0:10:49.679 either brilliant or crazy. Hog was then a Mackenzie partner 0:10:49.720 --> 0:10:52.400 with a medical degree, and he was interested in doing 0:10:52.520 --> 0:10:56.839 something that would have more societal impact. He slowly came 0:10:56.880 --> 0:11:01.080 around to Boncell's view that mRNA therapy, if worked, was 0:11:01.120 --> 0:11:05.800 really going to transform medicine. The concept behind m RNA 0:11:06.000 --> 0:11:09.800 vaccines is simple. When the shots bring those protein making 0:11:09.840 --> 0:11:14.880 instructions to cells, they effectively turned them into microscopic vaccine 0:11:14.880 --> 0:11:18.959 factories in their own right. This allows developers to streamline 0:11:19.000 --> 0:11:24.160 what is normally a messy manufacturing process. Many flu vaccines, 0:11:24.200 --> 0:11:28.160 for example, are made inside chicken eggs, and even newer 0:11:28.200 --> 0:11:33.920 genetically engineered vaccines still require growing viral proteins inside vats 0:11:33.960 --> 0:11:39.440 of live sales. Bypassing such steps lets mRNA vaccine manufacturers 0:11:39.640 --> 0:11:43.479 shift gears fairly quickly. It also appears to be relatively 0:11:43.640 --> 0:11:48.920 easy for them to make complicated vaccines involving multiple viral proteins. 0:11:49.800 --> 0:11:53.160 Everything with m RNA is just simpler, says Barney Graham, 0:11:53.280 --> 0:11:56.760 Deputy director of the Vaccine Research Center at the National 0:11:56.760 --> 0:12:00.920 Institute of Allergy and Infectious Diseases WHO LAB has been 0:12:00.960 --> 0:12:06.680 formally collaborating with Moderna since seventeen. For me, making vaccines 0:12:06.760 --> 0:12:09.400 that are as simple as possible is the way to go, 0:12:09.960 --> 0:12:13.719 Graham says. Gene based shots such as m RNA vaccines 0:12:14.000 --> 0:12:18.040 are particularly well suited to fighting viruses because they seem 0:12:18.080 --> 0:12:20.960 to be adept at producing the so called killer T 0:12:21.160 --> 0:12:26.000 cells that destroy virus infected cells. Before MODERNA could create 0:12:26.040 --> 0:12:29.560 an mRNA based product, it had to crack the problem 0:12:29.600 --> 0:12:32.680 of how to protect the molecule from the body's defense 0:12:32.720 --> 0:12:36.640 systems by modifying the RNA. The pen researchers had figured 0:12:36.679 --> 0:12:40.640 out how to dampen the hair trigger immune response it provoked, 0:12:41.080 --> 0:12:43.560 but their approach would be useless if it were broken 0:12:43.640 --> 0:12:46.920 down by enzymes before it could reach cells. The key 0:12:46.960 --> 0:12:49.840 to solving that problem turned out to be adding protective 0:12:49.880 --> 0:12:55.440 lipid nanoparticles to surround the mRNA molecules, essentially creating balls 0:12:55.480 --> 0:12:58.240 of fat with little bits of RNA mixed in there, 0:12:58.520 --> 0:13:02.600 says Carrie Bennatto, chemist who left asdra Zenica to join 0:13:02.679 --> 0:13:07.440 MODERNA in. When MODERNA started working on this approach in 0:13:08.840 --> 0:13:11.680 it had been tried mostly on much smaller types of 0:13:11.800 --> 0:13:16.320 RNA molecules, and there were concerns about side effects. People 0:13:16.320 --> 0:13:21.959 had decided they were toxic coaxes. Nanoparticles contained synthetic fats, 0:13:22.040 --> 0:13:25.000 and in early iterations, some of those fats tended to 0:13:25.080 --> 0:13:29.560 accumulate in cells, building up over time and potentially causing 0:13:29.679 --> 0:13:34.600 liver damage or other side effects. Beninato's assignment was to 0:13:34.679 --> 0:13:39.040 devise nanoparticles that could safely and efficiently carry out the 0:13:39.160 --> 0:13:43.280 m RNA into cells, release the playload, and then quickly 0:13:43.360 --> 0:13:47.400 break down. When she started, the chemistry involved in using 0:13:47.480 --> 0:13:51.240 nanoparticles with m RNA was so unexplored that there were 0:13:51.320 --> 0:13:55.280 few published scientific papers to guide her. She and her 0:13:55.320 --> 0:13:59.720 team made one tweek after another, pinpointing changes that improved 0:14:00.080 --> 0:14:06.439 lnerability without harming their ability to deliver mRNA. By Moderna 0:14:06.520 --> 0:14:10.320 had made a breakthrough finding a series of lipid molecules 0:14:10.360 --> 0:14:13.560 that fit the bill. Then it was off to the races. 0:14:13.600 --> 0:14:17.520 Ben and Otto recalls they patented the formulas and started 0:14:17.559 --> 0:14:21.400 deploying them in vaccines. In its early years, Moderna had 0:14:21.440 --> 0:14:25.960 focused on therapeutics, including programs for cancer, heart disease, and 0:14:26.040 --> 0:14:30.280 other lucrative areas. The company gradually turned to vaccines as 0:14:30.320 --> 0:14:33.480 Boncelle realized they would be the best way to prove 0:14:33.640 --> 0:14:38.040 mRNA technology worked. You have to inject only a couple 0:14:38.080 --> 0:14:43.120 of doses to stimulate a long lasting immune reaction. Working 0:14:43.120 --> 0:14:47.320 with Graham's team at NAIAD, Moderna began formulating a COVID 0:14:47.400 --> 0:14:51.520 vaccine as soon as Chinese scientists released the coronavirus RNA 0:14:51.640 --> 0:14:56.720 sequence in early January. Later that month, Bonzell asked his 0:14:56.800 --> 0:14:59.960 manufacturing chief what it would take to make a billion 0:15:00.120 --> 0:15:04.240 vaccine doses in one He looked at me like I 0:15:04.280 --> 0:15:08.240 was insane. Bon Cell recalls the Moderna plant had never 0:15:08.320 --> 0:15:11.120 made more than one hundred thousand doses of anything in 0:15:11.160 --> 0:15:14.840 a year. The US government agreed to pay nine hundred 0:15:14.920 --> 0:15:18.280 fifty five million dollars for the vaccine trials and initial 0:15:18.320 --> 0:15:22.120 small scale production, but bon Sell says he couldn't initially 0:15:22.200 --> 0:15:25.480 persuade any country to pay for a full scale up. 0:15:26.400 --> 0:15:29.560 Moderna instead raised one point three billion dollars in a 0:15:29.680 --> 0:15:33.600 May stock offering for the purpose. The move allowed the 0:15:33.600 --> 0:15:36.440 company to take its leap onto the world stage and 0:15:36.520 --> 0:15:41.040 laid the groundwork for what comes next. Moderna produces its 0:15:41.120 --> 0:15:44.080 nanoparticles and m R and A in a former Polaroid 0:15:44.120 --> 0:15:48.040 factory in the Boston suburb of Norwood, fifteen miles south 0:15:48.080 --> 0:15:52.520 of its headquarters. The plant, which opened in July, has 0:15:52.560 --> 0:15:56.320 been running around the clock since November. It looks less 0:15:56.360 --> 0:15:59.280 like a factory than a cross between a tech startup 0:15:59.320 --> 0:16:03.240 and a MOLECUA. Their biology lab, dozens of operations and 0:16:03.320 --> 0:16:07.200 quality control workers dressed in casual clothing, occupy a large 0:16:07.280 --> 0:16:10.640 warren of open layout desks in the front of the building. 0:16:11.240 --> 0:16:14.560 COVID vaccines are produced in clean rooms, some of which 0:16:14.600 --> 0:16:18.440 are visible behind glass panels in the back. There are 0:16:18.520 --> 0:16:21.160 nine of these clean rooms making the shot here, up 0:16:21.200 --> 0:16:24.880 from three in December, and six more are scheduled to 0:16:24.920 --> 0:16:27.720 be running by the end of the year. The suites, 0:16:27.720 --> 0:16:30.840 which are roughly one thousand square feet each, were built 0:16:30.880 --> 0:16:34.680 for flexibility. The process starts with pieces of DNA called 0:16:34.720 --> 0:16:38.880 plasmids that Moderna brings in from a contract manufacturer. These 0:16:38.920 --> 0:16:43.280 plasmids contain the genetic blueprint for the COVID nineteen spike protein. 0:16:44.000 --> 0:16:47.000 In one set of clean rooms, the spike protein DNA 0:16:47.160 --> 0:16:51.920 is synthesized into m RNA using a technique called vitro transcription. 0:16:52.440 --> 0:16:55.800 It's basically the laboratory version of the process that normally 0:16:55.800 --> 0:17:00.320 occurs in cell nuclei. The m RNA solution and can 0:17:00.360 --> 0:17:03.239 be made in a matter of hours, says Scott Nickerson, 0:17:03.800 --> 0:17:07.640 a senior vice president who oversees the site. It then 0:17:07.720 --> 0:17:12.920 takes several days to purify unreacted enzymes and other extraneous material. 0:17:14.040 --> 0:17:18.000 From there, the purified mRNA goes to a separate set 0:17:18.000 --> 0:17:21.600 of clean rooms, where workers spend another few days formulating 0:17:21.640 --> 0:17:25.960 it with lipid nanoparticles. The final product is frozen and 0:17:26.119 --> 0:17:31.240 sterile bioprocessing bags, encased in a protective shell, and shipped 0:17:31.240 --> 0:17:36.879 in temperature controlled trucks to Catalants plant in Bloomington, Indiana. There, 0:17:36.920 --> 0:17:40.720 the vaccine is deluded, put into vials, labeled, and shipped. 0:17:41.200 --> 0:17:44.960 When Moderna started making the COVID vaccine and commercial quantities 0:17:45.040 --> 0:17:48.359 last year, the process took as long as nineteen days 0:17:48.400 --> 0:17:51.480 to complete. Now it takes only ten days to prep 0:17:51.480 --> 0:17:55.359 a bat for shipping to Catalan. Last May, Moderna signed 0:17:55.359 --> 0:17:58.920 a ten year deal since expanded twice with Lonza Group, 0:17:59.160 --> 0:18:02.000 which is expected to produce the bulk of its European 0:18:02.119 --> 0:18:07.480 supply at factories in Switzerland and the Netherlands. Moderna also 0:18:07.560 --> 0:18:11.720 made packs this year with Sonofie, Samsung Biologics, and Thermo 0:18:11.800 --> 0:18:16.240 Fisher Scientific to bolster the vile filling capacity. Increasing so 0:18:16.400 --> 0:18:20.359 called phil finished capacity will become important. That's a greater 0:18:20.440 --> 0:18:24.240 share of the population is vaccinated and doctors can't find 0:18:24.359 --> 0:18:27.560 enough patients to use up the larger vials now in use, 0:18:27.920 --> 0:18:32.760 which contained between ten and fifteen doses. Moderna's production this 0:18:32.840 --> 0:18:36.720 year eight hundred million to one billion doses will amount 0:18:36.760 --> 0:18:40.000 to only about a third of Fiser and bion Tech's output. 0:18:40.800 --> 0:18:44.080 Fiser had one hundred times more people at the start 0:18:44.080 --> 0:18:48.159 of the pandemic, along with existing plants it could retool 0:18:48.240 --> 0:18:53.200 for vaccine production. Bond Sal says Moderna's headcount has almost 0:18:53.240 --> 0:18:57.479 doubled since last year to fift hundred Next year, with 0:18:57.520 --> 0:19:01.400 more capacity and a significant portion of its output potentially 0:19:01.480 --> 0:19:05.960 going to booster shots and pediatric formulations that use lower doses, 0:19:06.520 --> 0:19:09.399 the company and its partners expect to produce as many 0:19:09.480 --> 0:19:14.119 as three billion doses, approaching Fiser and bion Tech projected 0:19:14.920 --> 0:19:19.520 to supply of four billion if Novavax meets its production goals. 0:19:19.800 --> 0:19:24.080 Snopie's protein based vaccine also works, and companies such as 0:19:24.160 --> 0:19:28.600 Johnson and Johnson and Azra Zenica solve their manufacturing bottlenecks 0:19:28.640 --> 0:19:31.320 at some point next year, the world could shift from 0:19:31.320 --> 0:19:35.600 being desperately short of COVID shots to swimming in them. 0:19:35.640 --> 0:19:38.399 As the virus settles down to a more manageable threat 0:19:38.480 --> 0:19:42.600 over the next few years, COVID vaccine sales may decline, 0:19:42.960 --> 0:19:48.280 perhaps precipitously. Morning Star analyst Karen Anderson says this market 0:19:48.359 --> 0:19:52.600 could top out at seventy two billion dollars worldwide this year, 0:19:53.240 --> 0:19:57.159 slip to sixty five billion in two, and plummet to 0:19:57.359 --> 0:20:00.840 eight billion a year after that. The extent of the 0:20:00.880 --> 0:20:04.160 slide will depend on how many people need booster shots, 0:20:04.160 --> 0:20:07.800 how often, and whether Moderna, Fiser and others will be 0:20:07.840 --> 0:20:11.199 able to raise prices to compensate for a smaller market. 0:20:12.119 --> 0:20:15.679 The science on booster shots is still unsettled. It's not 0:20:15.800 --> 0:20:18.800 clear on how often or even whether they'll be needed 0:20:18.840 --> 0:20:22.760 in large numbers. Moderna has three types of boosters in 0:20:22.840 --> 0:20:26.440 phase two trials, including a lower dose version of its 0:20:26.480 --> 0:20:30.800 existing vaccine, one booster that's been customized against the beta 0:20:30.880 --> 0:20:34.040 variant that was first spotted in South Africa, and a 0:20:34.119 --> 0:20:38.840 third that combines both. More variants can be added if necessary. 0:20:39.280 --> 0:20:42.680 The process for the beta booster went even faster than 0:20:42.720 --> 0:20:47.200 for the original shot. Design work started on January twenty second, 0:20:47.560 --> 0:20:51.840 with Moderna ultimately switching out some of the chemical letters 0:20:51.880 --> 0:20:56.120 in its original mRNA vaccine so they corresponded to the 0:20:56.160 --> 0:21:01.040 spike protein in the beta variant. Manufacturing began three days 0:21:01.119 --> 0:21:04.560 later and The first trial dose was administered on March tenth, 0:21:04.920 --> 0:21:08.160 only forty seven days and all compared with the sixty 0:21:08.320 --> 0:21:12.800 five for the main vaccine. Moderna is already cutting deals 0:21:12.800 --> 0:21:17.000 that encompass potential booster doses, including a June order from 0:21:17.040 --> 0:21:20.280 the US for two hundred million additional shots in late 0:21:21.480 --> 0:21:27.240 and early Despite the uncertain need for boosters, Bonzale's pitch 0:21:27.320 --> 0:21:31.080 is that it's best to be prepared for an evolving virus. 0:21:31.800 --> 0:21:35.280 At an investor conference in early June, he told everyone 0:21:35.400 --> 0:21:38.160 that the smart countries are saying, I'd rather be two 0:21:38.200 --> 0:21:42.720 months too early than two months late. Beyond COVID, most 0:21:42.760 --> 0:21:47.520 of Moderna's experimental vaccines remain in early stages of human trials. 0:21:47.560 --> 0:21:51.600 An exception is the shot for psyto megalovirus. No vaccine 0:21:51.640 --> 0:21:54.360 exists for this virus now, and the shot could turn 0:21:54.400 --> 0:21:58.359 into a multibillion dollar product if it works. Moderna also 0:21:58.400 --> 0:22:01.879 plans human trials this year of a vaccine against another 0:22:01.960 --> 0:22:08.840 complicated pathogen, epstein bar virus, which causes mononucleosis. Influenza is 0:22:08.880 --> 0:22:11.679 an obvious target at a shot for that could be 0:22:11.760 --> 0:22:15.840 combined with COVID boosters, locking them into an existing annual 0:22:15.960 --> 0:22:20.080 market with the fiser BioNTech Alliance, also slated to start 0:22:20.200 --> 0:22:23.920 trials on a flu shot later this year. Researchers say 0:22:23.960 --> 0:22:27.880 they're hoping the mRNA vaccines can improve on existing versions, 0:22:28.320 --> 0:22:32.679 which must sometimes begin production six months in advance based 0:22:32.680 --> 0:22:36.480 on experts assessment of which strains are likely to circulate. 0:22:37.400 --> 0:22:41.439 The shorter lead times required to make mRNA shots could, 0:22:41.520 --> 0:22:45.320 in theory, let health officials more closely match flu strains 0:22:45.640 --> 0:22:51.520 and improve upon typical forty to sixt efficacy rates. The 0:22:51.640 --> 0:22:54.760 m RNA vaccines have a very high likelihood of being 0:22:54.960 --> 0:22:58.359 better than the egg based vaccines we use now, says 0:22:58.440 --> 0:23:02.040 Andrew pocash A Virology just that JOHNS. Hopkins, Bloomberg School 0:23:02.080 --> 0:23:05.399 of Public Health. He adds that the shorter lead times 0:23:05.440 --> 0:23:09.040 could shave off months from the process, but he notes 0:23:09.080 --> 0:23:11.919 that it's an open question whether there would be a 0:23:11.960 --> 0:23:15.840 good economic case for m RNA based flu vaccines if 0:23:15.840 --> 0:23:19.440 they turn out to be more expensive and only modestly 0:23:19.520 --> 0:23:23.200 better than the old ones. MODERNA is also targeting a 0:23:23.240 --> 0:23:28.960 few nasty respiratory viruses that don't have vaccines. These include 0:23:29.000 --> 0:23:33.119 mennuma virus, which can lead to hospitalization and infants, and 0:23:33.280 --> 0:23:37.600 respiratory sencidal virus, which causes more than one d seventy 0:23:37.640 --> 0:23:42.320 five thousand US hospitalizations annually in the elderly and about 0:23:42.400 --> 0:23:46.200 fifty thousand more in young children. In the latter case, 0:23:46.320 --> 0:23:50.000 Moderna's vaccine will be competing with efforts at Glaxo Smith, Klein, 0:23:50.320 --> 0:23:53.760 and Johnson and Johnson that draw on other technologies and 0:23:53.840 --> 0:23:58.040 are further ahead. Hoak says Moderna could combine as many 0:23:58.119 --> 0:24:00.960 as a dozen or more viral strays in one shot. 0:24:01.480 --> 0:24:04.400 The goal is a seasonal vaccine that eliminates the majority 0:24:04.440 --> 0:24:07.760 of the respiratory viral diseases that we all suffer from. 0:24:07.800 --> 0:24:10.959 He says, the only way that we're really going to 0:24:11.000 --> 0:24:15.679 get good broad population immunity against these respiratory viruses is 0:24:15.720 --> 0:24:18.240 if we can make it feel like your flu shot. 0:24:18.840 --> 0:24:22.280 The concept makes sense on paper, according to Tony Moody, 0:24:22.400 --> 0:24:26.560 a physician researcher at the Duke Human Vaccine Institute, which 0:24:26.560 --> 0:24:31.240 is working on mRNA based flu vaccines. Combinations are one 0:24:31.280 --> 0:24:35.120 of the strengths of the technology. He says he estimates 0:24:35.200 --> 0:24:37.800 that it would cost only a few dollars more per 0:24:37.880 --> 0:24:41.800 shot to add the necessary mRNA for a given viral target. 0:24:42.440 --> 0:24:44.560 If you could get a combo shot that gives you 0:24:44.600 --> 0:24:48.040 a degree of protection against a lot of respiratory viruses. 0:24:48.600 --> 0:24:50.880 I think there would be a market for that, He says. 0:24:51.640 --> 0:24:54.760 It won't be fast or easy. Researchers will first have 0:24:54.920 --> 0:24:58.919 to show that the individual vaccines work and then perform 0:24:59.000 --> 0:25:04.320 studies showing at complex combinations don't compromise efficacy or result 0:25:04.400 --> 0:25:08.760 in troublesome side effects. To realize its vision, Moderna will 0:25:08.800 --> 0:25:12.800 have to move quickly. Competitors are investing heavily to catch up. 0:25:13.320 --> 0:25:16.480 Snophie said in late June it would spend four D 0:25:16.680 --> 0:25:21.320 seventy five million dollars annually on mRNA research, focusing on 0:25:21.359 --> 0:25:26.000 stable vaccines with few side effects, with emergency authorizations unlikely. 0:25:26.040 --> 0:25:29.840 In the future, considerations such as side effects and convenience 0:25:29.880 --> 0:25:34.199 will also assume new prominence. Moderna is working on eliminating 0:25:34.200 --> 0:25:38.840 the complicated refrigeration requirements of its COVID shot. Future products 0:25:38.880 --> 0:25:41.320 will also have to find ways to reduce the high 0:25:41.440 --> 0:25:45.399 rates of fatigue, headache, and muscle pain produced by the shot. 0:25:46.200 --> 0:25:49.320 For the boosters, the company is testing lower doses, which 0:25:49.400 --> 0:25:54.040 may help how broadly mRNA can expand beyond vaccines into 0:25:54.080 --> 0:25:58.119 the far larger and more lucrative therapeutics market remains to 0:25:58.160 --> 0:26:02.080 be seen. There will be additional technical hurdles to surmount. 0:26:02.600 --> 0:26:06.040 To treat chronic diseases, for example, companies will have to 0:26:06.119 --> 0:26:09.080 prove that they can deliver the therapies to the target 0:26:09.240 --> 0:26:13.560 organs and that m RNA can be administered safely. And 0:26:13.640 --> 0:26:17.720 to develop cancer vaccines, mRNA researchers will have to solve 0:26:17.760 --> 0:26:21.280 the thorny problem of teaching the immune system to distinguish 0:26:21.320 --> 0:26:27.080 between specific tumors and healthy sales. Many previous approaches have failed. 0:26:27.600 --> 0:26:31.119 The good news is that mRNA's adaptability also makes it 0:26:31.160 --> 0:26:35.200 easier to try out many possibilities. Within a few years, 0:26:35.280 --> 0:26:39.080 moderna could have sixty drugs and vaccines either in human 0:26:39.160 --> 0:26:42.800 trials or nearing them. According to bond Sell, if it 0:26:42.840 --> 0:26:46.280 works out the way he hopes, mRNA will make inventing 0:26:46.359 --> 0:26:51.199 vaccines and drugs a bit more like creating software. We 0:26:51.359 --> 0:26:54.760 use the same for letter code for every vaccine and drug. 0:26:54.800 --> 0:26:58.240 Bond Sales says, we can scale the number of products 0:26:58.280 --> 0:27:00.880