393: A conversation with the 'godfather' of biotech

[Music] Welcome to this week's episode of The Readout Loud, a weekly biotech podcast from STAT. I'm Elaine Chen. And I'm Adam Forrestine, Allison D'Angeles is out this week. It's Friday, March 20th. We have dropped this week's episode one day later than normal because we wanted to bring you a special conversation with Stelios Papadopolis, aka the godfather of biotech. Yeah, Stelios sat down for an onstage chat with our colleague Damian Gardet yesterday afternoon during STAT's Breakthrough Summit East Event in New York City. You'll get a chance to hear that conversation here, right after we're from our sponsor and a recap of this week's news. [Music] I'm Stetper and Studio Editor, Jesse McQuarrers, and I'm talking with Dr. Fred Applebaum, Executive Vice President at Fredhutch Cancer Center. Dr. Applebaum, how has the work done over the past 50 years of Fredhutch impacted how we treat cancer today? About 50 years ago, Don Thomas and our team showed that marrow transplantation was possible, which enabled us to cure almost every marrow-based disease. Today, over 100,000 people worldwide undergo a marrow transplant every year. Going forward, we're developing even better immune therapies. Antibase therapies, cell-based therapies that harness the power of the human immune system to eradicate cancer. For more information on Fredhutch Cancer Center, visit Fredhutch.org/lookbeyond. So, Elaine, it was a relatively tame week for biotech news. We did get some new data on weight loss drugs from structure, therapeutics, and Eli Lilly, because, you know, what would a week be without more obesity news? Tell us a little bit more about what we saw. Yes, so we'll start with structure. They reported some new phase 2 data from its candidate that targets the Amelene hormone. On first glance, the top line data, 16% weight loss at 44 weeks, that does seem like a pretty efficacious drug, the stock spiked on the news. But there are some caveats. That was the efficacy estimate, so basically the efficacy when you are analyzing basically only those who stayed on treatment. There were, in fact, a lot of discontinuations in an earlier data release, structure had said that in the titration phase of this study, 28% of treated patients discontinued due to side effects. So, if you were to calculate the actual efficacy taking into account those discontinuations, I assume the actual efficacy would be lower. Also, just that amount of discontinuations is concerning. How appealing would the drug really be if it leads to that many discontinuations? I also want to note that structure and its most recent data release did not bring up that discontinuation number. We had to go back to look at an earlier release. So, I feel like that's an important number that they should have mentioned. Structure also explored the question, "Okay, what if we start out a lower starting dose? Does that help with tolerability?" They did release preliminary results from a different study that did start with a lower dose, and it does seem like it helped with tolerability after about 20 weeks. The discontinuation rate due to side effects was 3.4%. But it seems like there was a lot lower efficacy because at that time point, the weight loss was about 6.8%. In general, I feel like the press release was not very straightforward. The one that they released this week. And Adam, as you and I have always said, if data is not presented in a straightforward way, that always brings questions about how good the data is. I think what's interesting about this is that sometimes the numbers start to get blurred. You see all these numbers, weight loss numbers, and treatment discontinuations. But I wonder, because you look at more of these data than just about anybody gets stat. I wonder when you see these press releases, what are you looking for? It does seem like the stuff that they don't tell you is almost as important if not more important than the stuff that they do tell you. A lot of times companies present the efficacy estimate, but we really want to know the treatment regimen estimate, which is the efficacy considering all participants, including those who discontinued. That is what the FDA considers when they're reviewing drugs. And that's what allows helps us to be able to compare drugs across trials more easily. And with that, we also want to see discontinuation rates, specific rates of side effects, which oftentimes companies don't disclose in top line data. I feel like this is just a plea for companies to please just present data as they are straightforwardly. Because at the end of the day, we're going to see the full data. We're going to see the data for what it is. So just present it to us as it is. Don't try to choose certain data, cherry pick certain data. Just just give us the data. So moving on, we also saw data this week from Lily from their so-called triple G drug. LA, and what did you see there? Yeah, so this is a rather true tide. Lily's triple G drug that targets three hormones, GLP1, GIP and glucagon. It's seen as perhaps one of the most potent way lost drugs that are that's in late stage development right now. In this trial, it was a type two diabetes trial. The drug led to up to two percentage point reduction on HBA1C, a measure of blood sugar. But more notably, it led to pretty significant weight loss up to 15% weight loss. I think that may be the most weight loss we've seen in a diabetes drug trial. It's really notable because diabetes patients typically have a harder time losing weight on drugs than people who don't have diabetes. So that is very good news for people who have both diabetes and obesity, which the CDC estimates makes up about 60% of all adults in the US with type two diabetes. But when I saw the weight loss number, I did also start to wonder whether the drug is suitable for the whole population of type two diabetes people, including those who aren't obese. The trial was not focused just on people who were obese. It enrolled anyone with a BMI over 23, which is considered a normal weight BMI. And Lily would not disclose data on what percentage of the trial was not obese, what their specific weight loss numbers were. So those are all questions that I have before we see the full data. So Elena, you're telling me that even Eli Lilly sheds the way that they disclose and report data on obesity drugs? I think all companies do to some extent. I mean, I guess they have to keep some data withheld because you know they're going to present them in scientific congresses or whatnot. But yeah, I think all companies to some extent are not always very transparent. So there was another notable obesity related event this week notable. I guess for its rarity, a Wall Street cell rating on Eli Lilly stock HSBC Farm Analyst Rajesh Kumar downgraded Lily on Tuesday. Elena, what is his beef with Eli Lilly? Yeah, this was interesting because we've talked about a lot before on this podcast. It seems like so many analysts out there really love Lily and kind of almost it feels like think that Lily can do no wrong. These HSBC analysts though, they say that Lily is put price to perfection. So there are several factors in their argument. One is they think the obesity drug market won't be as big as a lot of investors are anticipating. They also think investors are too optimistic on the launch of Lily's GLP1 pill or Ferglipron, which we expect to be approved probably very soon. They say that people are overestimating the number of people who will stay on the pill consistently. And then lastly, I thought this was maybe the most interesting is the analyst questions Lily's reliance on the direct to consumer cash market. That has been a point of differentiation for Lily. They were the earliest to really start growing that cash channel and analysts have pointed to that as you know a reason for strength for Lily. But these analysts said that because patients are paying out of pocket by themselves in the cash channel, the cash market is very sensitive to the economic cycle. So if there's an economic downturn, that means that many people will no longer be able to afford to pay for these drugs out of pocket. So that is a vulnerability. And that seems to be one of the key reasons why there are such diverging forecasts from Lily and Novo. If you might recall from the last earnings cycle, Novo gave a pretty negative outlook while Lily gave a very positive outlook. So I mentioned this to you earlier, but my idea is that Lily should start a credit, have a credit card. They should have like a weight loss credit card. And then people can just charge their weight loss drugs to the credit card and Lily can earn 25% interest on those cards. Yeah, they can do a car in a situation too. What could go wrong? Just the promise, if you stop paying for your car, you stop car payments, they can repossess the car. But if you don't pay your obesity credit card, what do they take away? Like how does that work? That could be a problem. Yeah. They could probably still also repossess your card. In other FDA news this week, we were seeing more staff departures. Adam Sherwatt, the director of the Office of Infectious Diseases, is leaving the agency in early April. Also leaving the FDA Andrew LeBuff, Associate Senate Director for regulatory strategy, and Julie Tomano, Deputy Director in the Division of Gastroenterology. The departures were reported this week by our colleague Lizzie Lawrence. And lastly, Johnson and Johnson won US approval for a daily psoriasis pill that rivals the benefits of injectable medicines and could reshape one of the most competitive deals in the pharma industry. The drug IcoTide is approved patients over the age of 12 with moderate to severe plaque psoriasis. It's designed to mimic the effects of top-selling injectable treatments, including Abbe's SkyRizzi and J&J's own trimphio. Stelios Pappadopoulos has seen it all in biotech. From the industry's backwater beginnings to the boom in bus cycles that have minted millionaires and ruin careers. Over a career spanning more than four decades, Stelios has built a reputation as a creative dealmaker, a wise advisor to CEOs, entrepreneurs, and boards, and as an enthusiastic historian of the biotech industry, his nickname, the Godfather, speaks to the level of respect and admiration he's earned from his peers and those he's mentored. On Thursday afternoon, Stelios sat down for a conversation with our colleague Damian Garde at stats breakthrough summit east of N in New York City. The topics just about everything. The FDA, China, the current state of pharma, and what it takes for smaller biotech companies to grow into the next vertex or a general. Replease to share their talk with Redout Loud listeners. Enjoy. Thank you Stelios for making time today. I didn't plan this session to aggressively because I wanted to replicate. I know people seek your counsel quite often and so I thought I wonder if I can replicate that experience in a more public setting to bear with me but I wanted to start with the FDA. It seems like each week, if not each day, there's a new personnel upheaval or a drug review controversy or questionable directives and my question basically how bad is it going and what are the risks at place if this kind of pattern persists? Before I answer the question, how do you pronounce your last name? Garde, Garde, the middle one. It's Spanish but there's no accent on the E. Very good. Okay, we're sold another mystery. So we get to go. The FDA, look, I will say this. I never met Chris Clump before. I saw him on television but he's my hero. This guy is amazing. I mean, he's knowledgeable, he's passionate, he's articulate. I mean, listening to him for a moment, I thought the FDA was doing okay. He was a good agency. But seriously, I tell you, there's actually in my mind, I hope that a sensible, capable, dedicated person like him is in positions in a position of influence because otherwise, if you just imagine for a moment to your question now, if FDA were a company and the CEO gets on TV and talks about a bunch of stuff and they make good sense, they're good messages but then you see the outcomes and they're not the same as the pronouncements. Yes, senior executive gets a job and tries to settle scores with other people from his previous life and leaves. Another one comes, then goes, comes back, goes again. I mean, it's just, if FDA were a company, you know, what would happen? Everybody would be shorting the stock. It's scary. It's beyond scary. It's, it's amazing that none of us are raising our voices enough to complain, to register or dissatisfaction. And I think all of us, there are really two reasons for that and I should turn this way to be fair to the whole world. One is real and scared for attribution if we go public with up-or-nouncements. And the other is the expectation that somehow magically, whether it's the midterms or, you know, two and a half years from now, all that bad dream goes away and we're back to normal. Maybe. But it's easier as we all know to destroy them to build. So it will take a while. A lot of very good people. I think Klomb was absolutely right. There's a really great collection of individuals of extreme talent who could do very well in commerce, in places where they could make a lot more money, have influence, who choose to do public service and stay at FTA and we'll lose in many of them. So I'm concerned. I'm beyond concerned. So you mentioned it's, you know, it's more, it's easier to destroy than it is to rebuild. If there were whatever magic lever people might imagine to change leadership at the FTA, at what point is it beyond repair? Is there a point at which it's beyond repair? And what do you imagine it would take to get it back on track? Well, for one thing, I think we all appreciate the problem is not just FTA and leadership. There's the broader healthcare environment. And again, I'm not privy to plans at the highest levels for who's going to be secretary, who's going to run CGT and all that. So, but let's assume for a moment magically, there is new health leadership in the country. Rehiring a great collection of individuals that have been lost, they've left the agency's plural. It isn't just FTA, takes years. Now, maybe along the way as they're destroying things, you know, some things need to be broken to get fixed. There's a lot of things that are wrong in McCarrie. Says a lot of right things about accelerating, you know, one trial rather than two trials. And by the way, there's no great statute that FTA that said you need two trials to get approval. It's a judgment call. And if you have good mechanistic explanation, if you have compelling data, it's an important disease. Single trial gets you approved time and again, time and again. So that's more noise. On the rear diseases, they keep on talking about what they're going to do, but in practice, they keep on asking for control arms, along the trials and your follow-ups. So it is hard to reconcile what you hear and what happens. Now, they're talking about the IRBs. Absolutely an enormous problem. They said do-so-review boards. Typically, if you're going to commence a trial, you could easily spend six at least to 12 months negotiating with medical centers with the IRB. Sometimes they also have a science committee. And all of them, if you actually sit in the back room and you listen, they sit in the second guessing, the sponsor, and FTA. It's an FTA approved protocol and our group of well-meaning, intelligent, caring physicians who've never developed a drug in their lives have opinions on how the trial should be persecuted. The problem is FTA is no jurisdiction of the IRBs. In fact, no one has global jurisdiction over the IRBs. So it will take some much broader grassroots efforts to rectify this because this is clearly, you know, Pierre Vibrotor, said, "Well, China and all this concerns and I won't be able to those points you know, you read the papers, you sit in, you all appreciate that." But that is clearly an advantage China has in moving drugs into the clinic. I wondered on that topic, everybody knows the statistics of the larger share of global clinical trials are conducted in China, the percentage of new molecules being licensed from companies in the United States. From China, I wonder, I mean, you gave that out and is there a point at which the next genetic is Chinese? And what implications would that have for biotech as it exists to this point? Without a doubt whatsoever. Look, I mean, the trends is pretty clear. They decided some years ago, with a sort of global way of thinking, to bring back a whole bunch of talented experts, given the conditions and support, that would allow the ability to do good science in an academic setting, and also have commercial interest and companies on the side. Very much like what do we do here? There are some academic scientists, you know, all know who they are. You know, there's a particular guy, friend of mine, great guy. He may have started a hundred companies. I mean, think of this and he's a professor, a member of Academy, he's done all of that. So they've done all of that. Right now, we at the stage where they seem to be developing interesting compounds, everybody calls them, me too equivalent or whatever, and everybody's shopping over there. You know, by the way, if you again, you could always have gone back to history, but. -Side acquisition. -Couple letter. Guys, here's a fact. I mean, this really precious slice of life that have been around long enough to have seen a lot, but I'm not so old as to be demented. So I'm not sure there's a six-month slice or a six-year slice, but there's a last forever. So endure and enjoy. If you go back and you look at the way the farmer industry has evolved, for many years, in the '67s and '80s, the typical US-based multinational would be shopping around Europe and Japan for interesting compounds. And a lot of these compounds came from there that got developed. And then, as in the '80s, the biotech industry started becoming the farm league or whatever they called them, the AAA, you know, of, this is baseball, you're not American. The AAA of a farmer, they started getting compounds, you know, out of there. Now they all go to China. This is the new biotech industry. And that's fine, no problem. The VCs, because the animals that pursue capital flows intelligently. So they're now investing there to start companies that would sell to somebody else. And isn't just China, by the way. If you look at Pfizer's acquisition of METSERA, the obesity company, the compounds came out of South Korea and the other peptide methodology out of the UK. So the rest of the world, more or less, is looking to find ways to capitalize on innovation. And that's fine. Now what happens is all this is fine. No problem. Whether the drug came out of biotech company in Michigan or a Chinese company who cares, if it's a good drug, it's developed. At some point, one of these rapidly growing Chinese companies that has a family of innovation and a family of commercial success will come and buy a METS-sized US-based company to acquire a commercial US footprint. It's going to happen. It's mathematically certain. It probably will be in my lifetime. And my mother's 96, so I got a few more years left with good genes. And then what is going to happen is they will grow. And they will become major multinationals. Now is that important? Is it scary? Probably not. Except for one thing. Let's assume for a moment there's a global COVID-like crisis. Okay? And let's assume that this innovative and large global Chinese origin company develops a unique vaccine or pharmaceutical product. And let's assume it's limited supplies. The Chinese government has strategic visions about conquering and dominating the world. All assumptions. Could you envision a situation by which that precious drug may not be delivered to US citizens and be limited to China first? Don't be surprised. They will talk in the early months of the COVID vaccines about US manufactured doses of vaccines remaining for US consumption first and not be exported. So these things are realistic. And my word about this, I'm not because of the other day when China comes to China, it's an equal footing with the US in terms of sophistication, size, global domination. They become, they already quite rely on each other. They own so much of our government debt. If we go under, they're going to go under. You know, each other's creator trading partner. So I'm not really all that worried as much as people are. But I'm uploading all the excitement. There's a lot of smart people there and smart people are good people. So I'm not worried. I wonder, because there are people who are worried or who would perceive the vision of the future you just described as a disaster for the United States as they perceive it to want to continue. Does it concern you that those people, many of whom are in our government right now, will probably persist? Will take action to prevent that happening that in itself will be deleterious. For example, imposing, you know, there are capital controls basically on what the US, what US investors can invest in in other nations overseas in certain sectors. If they were to add biotech to that, for example, and extend it as part of national security, and we all just become more nationalist in terms of the life sciences. Is that something on your radar? Like, what might that be? I'm not all that worried about this, because I think it's extremely difficult to control these things on a nationalistic basis. Now going back in 1991, I was commissioned along with half a dozen other individuals, by the Department of Commerce, under the auspices of the National Academy of Science, to do a study to assess the threat of Japanese domination in biotechnology. Now why? Because it was not long prior to that that the Japanese had formed a fairly dominant position in the electronics, consumer electronics business, you know, with videotapes and, you know, walk months and little radius and all that. And they were developing prowess and size and clout in the automotive industry. So a bunch of people in the Department of Commerce got alarmed and they wanted us to create a document that would be the basis for policy making. I had already seen the phenomenon of experience in Japan because at the time I was an investment banker at a firm called Payne Wharver that was to a large extent owned by a Japanese company. So I was going to Japan a lot and I had some pretty good idea of how they did business there. And the sort of flavor of our business in terms of innovation and flexibility, capital flows, lack of central planning and all that, did nothing compatible with what Japan was doing. And that's where China found the secret. They have so like central dogma, but not specific individual planning or every activity. People are just running loose, doing some stupid things sometimes. But that's what it takes to get there. So I'm not all that worried that the policy makers will be able to invent and then implement instruments that would portray global exchange of ideas. You know, we've spoken in the past about how, I don't know if it's a natural law, but it's these observable in history that major pharmaceutical companies tend to reach some kind of revenue plateau based on some great invention or blockbuster drug and then struggle to maintain top line growth or even just maintain that level. And I wondered, is that kind of a natural law? Like are we witnessing in this like great pipeline cliff era that we are apparently embarking on with major pharmaceutical companies? Are there inevitable declines here? Like are they forced to kind of replicate this process until they either have to merge with one another or run into some other kind of major catalyst? Yeah, that's a very fundamental question for the business. There isn't a natural plateau which is an absolute number which is the same forever. It's a never growing number. But essentially what it is is, you know, I think you all appreciate this. It's extremely difficult to systematize what an otherwise is a stochastic process. By the way, I'm a huge believer of data science. You know, I'm back in the 70s when I was a graduate student. I was sort of like coding Fortran on IBM 360s. I mean, I've been in this world forever and I find all these new approaches fascinating. But if what we think we're going to get out of AI is with the systematized drug discovery, we're fooling ourselves because the moment you systematize it, no one's going to do any better. Everybody would be doing it. And if you look at the history of any individual drug, every event and every big drug, there's always this unique case of intuition, you know, sort of unusual thinking, counterintuitive decisions and approaches. And that's how you get to the great drugs because if everybody could see the great drug, that would be there. For instance, you know, what is everybody's favorite discussion nowadays, obesity, okay? All these ellipse Gibbs, triple G's and all of that. Now think of this for a moment. All of these science started at least 20 years ago, 30 years ago by a small company in San Diego called Amelene. They made it deal with lily, typical alliance. They also made it similar lines with J&J. Then Bristol bought Amelene the company and later on Bristol sold all these obesity related assets to AstraZeneca. Now here we are today. How much is AstraZeneca done in obesity? Or Bristol Myers or J&J? Next to nothing. Lily, amazing. And why did this happen? Well, I suspect to a large extent because John Lacklider, the prior CEO, was a very insightful person and there must have been one or two or three individuals in science who believed in this and kept on pressing forward. And you go time in again if you look at the great case of vertex dominant in the world of cystic fibrosis, how did this come to be? There was a tiny company in San Diego called Aurora. In 2003, vertex border Aurora. Why did it buy Aurora? Aurora had this thing called the beast. It was something a piece of equipment as big as half this room and it was a high throughput screening system. And vertex was developed with small molecules and they wanted to use all of that. So the border Aurora for the beast. Some of them within Aurora in some corner was again at Paul Dingo Lesco who was doing work on CFTR and cystic fibrosis and all of that and you know transport to the plasma memory [BLANK_AUDIO] and all that, and he kept on doing it. And all of a sudden, all these great drugs of synthetic fibrosis came out of that work. Nobody bought the company for that reason. Nobody assumed it was going to be value creating. And it's always some renegade, some rogue guy, particularly intelligent, insightful, and lucky. A lot of rogue intelligence are guys that don't get that luck to stumble on the great molecule or great biology. So if that we believe is the way great drugs get discovered and developed, then it is going to be inevitable because can somebody assemble a group of individuals? Look, the experiment is lily. If anybody can do it lily-n-i as you heard before from lily, they have the runway, the capital, and the inside. They're smart people. Can they create a self-sustaining organization that can keep on discovering great drugs? The problem, though, is the bigger you are at this point for lily, a billion dollar drug is rounding error. It's not going to be because, look, they're investors at the end of the day. And investors want to sit up line and bottom line growth. And if you're doing already 20, 30, 50, 60 billion of sales, another billion is nothing. Now if our little company would do nothing, 200 million is a great drug. Somebody in some conversation already today, the question was whether the industry is moving away from blockbuster to pick a portfolio of smaller drugs. It's inevitable. You cannot move away from blockbusters. Every single company in this business rises to fame and greatness, pretty much in the back of a single drug. By the way, there was a question before about blockbusters. The first blockbuster in the industry was in 1975. It was Tagamit, the ancient antagonist. It was for prior to Tagamit, if you had so-called bleeding ulcers, you went to the hospital for surgery. And these drugs were magical. So in my spare time, which I've got plenty, I tracked at one point the ranking by a market cap of every former company from 1950 to the year 2000 to watch the shifts in prominence. By the way, who will tell me and I'd be hugely impressed? What company are the biggest market capitalization, stock market value in the farmer industry in 1950? How many of you were born in 1950? Nobody. OK. Tell me. Probably atomic insert of a company in bars that had been charged. No. I don't even know that company. I'm a baritone being sort of like a pseudo-historian of the industry that I wouldn't know that company. But that's not a drug company, is it? Well, they produce something called "reunue act" that I do. No, there's no way they were the biggest. OK. That later, I know where to begin. There's got a name. OK. No, there was nuclear pharmacy company. No. The leader was Park Davis. Believe it or not. Park Davis is a great history of science. It was then acquired by Warner Lambert. It was then acquired by Pfizer. But the Park Davis people were particularly proud of themselves and their history. And forever, within Warner Lambert, there were the Park Davis people, then the Adams people, the Ticklets, and all these other people. So in 1975, at that point, it was Smith Klein from Arsotaquels, rose from the bottom of the rankings to number one. And within three or four years, it dropped down again because another guy called Glacso developed a somewhat, you know, similar, probably better drug, the same category, and became the next blockbuster. So if you go forward after that, and whether the blockbuster was $1 billion, then now it's probably like $200 billion drugs now. Maybe the number now is $5 billion, whatever. But somebody made a very good definition. Then it was Matt who said, a blockbuster is a drug that essentially defines the company because it's so big. And that's the business we're in. And it's very hard. And can you imagine being a CEO of a big, pharma company? You got there because you're driven, you're company, you go to all the meetings, you're smart, and you want to control everything. You've got to be a control freak, you become CEO. If you're not, you don't become CEO. That's a given. And you call your head of sales, you say, look, if you need $100 million, how much more revenue can you get? He says, well, I'll give you $200. OK, go to the manufacturing guy. You want another $50 million? What are you going to give them some efficiencies? He'll tell you. Then go to your earned digger, and he'll say, you need another $200 million? What are you going to give me? So if he's honest, he'll say, I have no idea where he'll lie to you. OK, and that drives you crazy if you're the CEO. And you want to systematize. You want to have agenomics driven drug discovery. You want to have so many compounds that go from freak clinical development to nomination. So many people face one. We don't have enough statistics in pharma. Any time somebody says to me, industry rates for success, how ridiculous is that? You're dealing average rates are meaningful when you're pure and experiment millions of times, not five or 10 times a year. So that's just irrelevant. What else? [LAUGHTER] Great point. I know you got to go. It's OK. I've got another three minutes. OK, we're good. All right. Do you want to have anybody ask a question? Do we let them try them in? Anybody with a question? The late in the middle. I hate to disagree with me, but please do. Hi, Suzanne Vibari, Med Shadow. And I hate to ask this question because I've heard everyone say it that it's a fact. But I don't really get it. You said early in this conversation that one study is enough to give the FDA. But isn't there like a replication, like process and problem in medical studies? They can't replicate original studies. So why should the FDA depend on one study to approve a drug? Right. Here's why. Because number one, there's this you'll need. If there's-- so all these things contribute to the decision. If there's a disease, which is untreated, there's great urgency to the part of the agency to look positive on something. If you have very compelling data-- and I'll give you an example in a moment or two-- that is important if you have a very good mechanistic explanation of why the drug should work. So I'll give you an example. Many years ago, I was the chairman of BioGen that, among other things, pursued-- and that was a unique case where, to in my tenure, we in license an early studies compound with developed in the clinic, we got approval, and we launched it. That was called spin raza. The compound is for a conditional spinal muscular atrophy. It's a congenital-- it's a genetic condition-- in the type one version, children die before the age of two. In the low in the mild versions, they can be capacitated in the late 20, 30, 40 years. We had to do a trial. It was a single trial. We agreed with FDA to be a placebo-controlled blind trial, because even though it pained us to know that some children with ascendance to death would not be getting placebo, but since we didn't have any experience with the drug, we thought it'd be important to test it for the rest of humankind. And the families agreed to that. But within six months of treatment, we were seeing the independent monitoring board were seeing market differences in performance. So in less than a year, FDA stopped the trial, crossed everybody over into the drug arm, and gave us approval in record time. So that's an extreme case of compelling data and unmet medical need. Now, if you're going to come to me with a novel anti-hypertensive that you may improve your blood pressure profile for the adverse population by 5%, you better do 20,000 patients per arm for me as an agency to be convinced, and no sane pharmaceutical company is going to go to a trial like that. It makes no sense. Neither there are special cases of hypertension, there are particularly a steering you need, different intervention, and yes, there are other drugs and all that. So it's a judgment called by the agency. Now, the other, the last one I would say is there are a lot of rare diseases, who are not only ethically, but practically, you cannot get enough patients to have real control arms. So you go with synthetic control arms, with historical data, and it's tougher, but that's what the agency is going to make a judgment call. - We do have a question from Rick Burke. - Hi, this is great, and I just want to recommend that everyone who has, everyone read Damien's landmark profile of you from four years ago, which was really a great entertaining read, and a fuel indulge in everything. - I'll say it's entertaining. I'll tell you in a moment something. - Okay, well, I want to ask you something. And forgive me for asking non-biotech question, but today, I'm going to ask you something. as a final question, there's an anecdote in this great profile that I want to hear from you because I don't know if it's like if you got the Lamb anecdote. Can you explain the San Diego Lamb and tell us the exact right story so we don't have to just assume Damien's-- Very quickly. I'll say this. Damien wrote a story which published in August of 2022 and I'll tell you why I know the date. Now I will say this for the prior three, four years started a particularly negative view of Bjarjan and seemed whenever they wrote about Bjarjan to have something of a negative slam on Bjarjan. So I get word out of the street that somebody at Stadis writing a profile of me and I'm saying, "Oh, shh, this is going to be." And now the one of those things where I'll be accused of whatever, he calls me. Nice guy politely. I answer the phone. Now I'm assuming it's going to be a bad story. So I say, "I'm not going to talk to you." I said, "You can go do whatever you want." And then somehow I think I came up with a great line on the spot which I've used the many times since. I said, "Look, I said I've got many flaws. Then it is not one of them." So I don't need any more, you know, and I think he quoted that. And then I'm getting this franticolsome people on the Wall Street and in the industry. This guy snooping around, I think questions about you. It's going to be a bad story, a bad story. So now I'm in Greece. My son is getting married September 3rd, 2022, at our home in Greece. Literally days, two, three days before the article comes out and somebody says to me, "It's out." Some really, again, I'm trying to come up with a place where it's going to be bad. It's like, great guy, but, there's no but. It's actually a pretty positive story. So the lamb. Many, many years ago, see if you, if you're Greek and you want to create, so like a team spirit, you wrote the lamb. That's how we do it. We do it for Easter. I'm getting ready. I've got 100 people coming to my house, April 12th, which is Greek Easter. So I had started a company in San Diego with some friends and we decided to have a lamb roast as a morale building and all that. And I'm something of an expert in lamb roast because I've been doing it for decades. So we show up and my friends are in San Diego where the lamb is going to be roasted and it's the evening of the day before and I smell the meat and doesn't smell good. So I said, "We're not going to poison the San Diego biotech community with bad lamb. That's not going to happen." So we need two things. We need a find a way to dispose it and two to find a new lamb. So the new lamb, somehow we managed to find some lamb rancher in somewhere in California and the next morning, somebody went, grabbed the lamb, brought it over and we did it. But now the question is, how do you get rid of a lamb in San Diego, La Jolla, in the middle of the evening? So what we did is, and there's not do the Godfather thing. So I chopped it up in pieces and put it in black garbage bags and a couple of them, not only Steve Holzman, many of you know Steve. Steve Holzman and I, a couple of others, we drove around San Diego going to the dumpsters or restaurants because we figured it would be the least likely place for badminton to be noted and we just dropped it in several, you know, pieces of the time and that's how it happened. So that's, it was pretty accurately described in the article. Thank you, everyone we need to stop. Thank you, John. Thank you. Thank you. That does it for another episode of The Readout Loud. Thank you to Hayes and the Benado for producing this week's episode. Our senior producer is Alissa Ambrose. Our executive producer is Rick Burke and our theme music is my Brian Joel. We'd love to hear from you tell us what you like about this week's episode, what you didn't like and whether you have your own Stelios story. You can do all that by sending us an email at [email protected]. And if you like what we do, leave a review or rating on Apple podcasts or whichever platform you use to get your podcasts. See you next week. [Music]