Wake-up haul: an Ozempic moment for the brain

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1:42Hello and welcome to The Intelligence from The Economist. I'm Jason Palmer. And I'm Rosie Bloor.

1:52Today on the show, why Japan has had such a weak startup scene, and how to beat procrastination and just get on with it.

2:06First up, though.

2:16Peptides are just huge at the moment. They're the P in GLP-1 drugs like Ozempic. But the pharma industry is, as always, looking for the next big thing. And our global business writer, Shailesh Chitnes, has been looking into which peptide might be it. There seems to be a lot of excitement in the pharmaceutical industry around a class of peptides. The new kid on the block is orexin. It's a neuropeptide that's found in the brain. And there is a new class of medicines called orexin agonists. Agonists are essentially medicines that mimic the action of a particular molecule. In this case, orexin's main job is to regulate wakefulness in a person.

2:59So the boundary between sleep and wakefulness, it is essentially the body's master switch that controls that. A whole new generation of drugs that are based on the orexin agonist are now approaching the market. And at least a few in the drug community are wondering whether this could be as big as the GLP medicines.

3:21So there are new drugs being developed around these things. Tell me about them. Yes, so just at the beginning of this month, a new drug called ovoperextone, which is made by Takeda, a Japanese pharmaceutical firm, was approved by the FDA to treat narcolepsy, which is a condition where the boundary between sleep and wakefulness is blurred. People who have narcolepsy typically without any indication or any warning may suddenly fall asleep. There's a more severe strain of narcolepsy, which is accompanied by cataplexy, where your muscles essentially freeze. So it's a pretty dangerous condition for people that suffer from it.

3:59And orexins have been found to be really impactful in treating it. And this particular medicine is based on an agonist of orexin, which we just talked about. But it's not just Takeda. There are a whole host of pharmaceutical companies that are actually working on drugs based off the orexin agonist. There's Alkermes, which is an Irish biotech firm that has a few candidates in the pipeline. And really the biggest is Eli Lilly, which I think all our listeners would probably know from their GLP drugs. They acquired a company called Centessa Pharmaceuticals, which is a biotech firm for a deal worth almost$7.8 billion.

4:38And Centessa has drugs in the pipeline that are based on the orexin agonist as well. So let's wind back a bit. Tell me how these things came to be known about in the first place. In the late 1990s, a group of researchers working independently converged on this neuropeptide. In fact, there's a very fascinating case of a researcher in Stanford called Dr. Emmanuel Mignot, who was studying the cause of narcolepsy in certain breeds of dogs, particularly Dobermans and Labradors. And these dogs had a very high propensity to inherit this particular disease, and he wanted to know why. and through various experiments he was able to narrow it down to a particular genetic mutation in their brain that made them not respond to the orexin molecule and so that gave very early clues that was then subsequently verified through human trials that people having narcolepsy essentially do not have enough orexin molecules in their brain and that set the drug makers on the path to actually create agonists which essentially mimic the activity of a particular molecule to create drugs based on that.

5:47So all of this is around treating narcolepsy? Yes, so that is the first step. Now narcolepsy is a fairly rare condition which afflicts between 1 in 1 ,000 to 1 in 2 ,000 people worldwide depending on various estimates. And what orexin does is by regulating the sleep and wakefulness cycle in the brain, it can actually help patients who suffer from narcolepsy control that boundary a lot better. But beyond that, it also has been shown in animal trials to be able to regulate other conditions in the brain, for example, the reward seeking behavior, motivation, things like that. And so drug makers hope that it can potentially be used to treat depression, ADHD, addictions, all other conditions that are based on these signals and they potentially could impact hundreds of millions of people.

6:42Now as I'm saying this I want to be very clear that all these downstream applications of orexin agonists they actually are very early. It needs to go through the rigorous clinical trials, large-scale patient testing before any of it actually makes it to the market. But again early indications and early clinical trials are quite hopeful in that direction. So on the basis of what we know now, what kind of market potential we might be talking about here? So I saw a report from Morgan Stanley, which is an investment bank, which estimated that these medicines could generate almost$16 billion a year by 2035.

7:17And just to compare it, the current crop of narcolepsy drugs have annual sales of around 3 billion. So by the virtue of these drugs being a lot more effective, they see the market purely for narcolepsy being much bigger. And of course, as you start to find more and more treatments and more and more conditions where this can be used, it has the potential to grow. It's hard not to draw a parallel then with the GLP drugs, which seem to have very wide application that have people very excited so that there is there's real potential here. Absolutely. And it's no coincidence that this is happening right at a time when GLP medicines have become these quote unquote everything drugs.

7:55They started out to treat diabetes very quickly, went into treating obesity, And from there on, drug makers continue to find new and new applications for it from treating heart conditions, kidney diseases. So it's no surprise that the comparisons are being made, but it's quite early. The signs are hopeful, but drug discovery has also been a graveyard of really great ideas that didn't make it through. We'll just have to wait and watch if this is one of them. Thanks very much for joining us, Sharlish. Thank you so much for having me.

8:29there is so much more to this story and lucky you dear subscriber shalesh joined babbage our sister show on science and tech to talk all about the history and potential future of orexins what was that first step where we actually saw orexin in use so it was very clear that Mouths without orexin, they cannot correctly maintain wakefulness, just like human patients with narcolepsy. What's that you say? You're not a subscriber? You don't get all of our deep dive weekly shows and kickback weekend intelligence? Oh dear. Hit pause right now, sign up. We'll wait. The link is in the show notes.

9:19In a world where AI is changing every role in every industry, knowing who actually has deep expertise matters more than ever. Upwork connects you with the highly skilled freelance professionals with proven track records, so you can hire with confidence. Upwork gives your business fast access to highly skilled specialists with deep expertise, so you can fill critical skill gaps, launch projects faster, and scale support up or down without committing to full-time headcount. With Business Plus, you can access the top 1 % of talent on Upwork. AI-powered shortlisting delivers a curated shortlist of top freelancers matched to your goals in under six hours.

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10:42Let me take you back to Tokyo in 1946. A young physicist named Morita Akio resigned from a teaching post at a top university and co-founded the Tokyo Telecommunications Engineering Corporation in a recently firebombed department store. A capital of$527 and a seven-man staff That was, in fact, all the resources we had with which to launch an enterprise. Today, you know that firm as Sony, and it's worth$140 billion. That same year, Honda was launched out of a ruined factory. As recently as the 1980s, SoftBank started as a small software distributor run by a 24-year-old. This month, it reported profits of more than$2 billion in a quarter.

11:29These are survivor-bias success stories, to be sure. But something about entrepreneurship does seem to have changed. Ever since the post-war period, when Japan produced world-best-reading companies from scrappy origins, the country seems to have lost its charm. Ethan Wu is our Asia business and finance editor and a co-host of our weekly subscriber-only show, Money Talks. One way to look at that is to see how many unicorns the country produces, which are startups worth over a billion dollars. Of the 1 ,400 unicorns that exist worldwide, only six today were born in Japan. Adjust that for population size, and it looks even worse.

12:12But why do you suppose that is, Ethan? Why the loss of charm? I think there are three main problems with Japan's startup ecosystem today. The first is very simple. It's just a shortage of capital. A shortage of capital willing to take risks on early ventures. Part of this is because venture capital, VC, in its modern incarnation is rather new in Japan. It barely existed until the mid-2010s. And while VC fundraising in Japan has increased rather precipitously in the past decade, that doesn't look too big when you compare it to pure markets. In addition to limited VC funding in Japan, this capital is also available unevenly.

12:50There's more available for early-stage startups, taking some kind of nascent idea and bringing it to commercial reality. But at the late stage, where startups take their commercial ideas and try to scale them up, there's a lot less of that late-stage capital available. This, in turn, limits the amount of interest that global VC investors have in Japan, the sort of investors who would write big checks for startups to take their ambitions global. Right, so not a whole lot of VC money in the pot and not a lot of it going global, but you said there were three problems. What else? Another problem is that in Japan, startups suffer from a low cultural standing.

13:25And this is no small deal. One survey by the Global Entrepreneurship Monitor found that just 24 % of Japanese consider entrepreneurship a desirable occupation compared to a global average of 67%. And this trickles down through the entire startup ecosystem. For startup founders, they're seen as taking unseemly risks with their time, with their livelihoods. That affects the way their friends, their peers, their parents perceive them. And for employees of these startups, they're also seen as taking something of a gamble. Particularly for those quitting from cushy jobs at well-established traditional Japanese companies, this sort of skepticism deters both founders and employees.

14:04And the third problem? The third problem, which is related to this low cultural standing, is that startups in Japan generally go public too quickly. Part of that is that venture capitalists in Japan are used to rushing to IPO. They want to cash out quickly, and they pressure their startups to get to that public listing as quickly as possible. And the other reason is that Japan historically has had too little M &A activity. The types of mergers and acquisitions that startups in the West would ultimately culminate toward. That means that firms in need of liquidity, who might not be able to get it from VCs who want them to go public, are forced to go public to get that cash.

14:43The result of this is a perception among investors and founders that Japan's initial public offering, its IPOs, are more equivalent to a U.S. Series B fundraising, the kind of modest intermediate stage fundraising round that generally in an American context would be associated with scaling up, not a big splashy debut in public markets. And you can see this in the numbers too. Japan, compared to peer countries, had the lowest amount of capital raised per IPO. But why is going public quickly such a problem here? Critics say that rushing to IPO distracts startups from pursuing long-term growth. Instead of laying the seeds for some kind of global expansion, for chasing that kind of 5x, 10x growth in revenue that startups need to attain really true global scale, they're instead trying to get their house in order to be fit for public consumption.

15:37And the result of this is that Japan's public markets for years have been riddled with tiny stagnant listings whose shares are going nowhere fast. At the end of 2025, the median market cap of firms debuting on the Tokyo Stock Exchange's growth market for up-and-coming firms was very small at just 10 billion yen or$61 million. And this is because there's not a lot of punishment. There are few sticks for these firms who debut at tiny market caps and trade nowhere. Delisting rules historically have been lax, and founders often receive social credibility for being on public markets, even if their performance from an investor perspective is poor.

16:22So is there a top-down fix here if Japan Inc. wants to have more unicorns? Yes, there is. And on this front, both the government and the Tokyo Stock Exchange, the TSE, have been making strong efforts. In 2022, the government unveiled a comprehensive startup plan to both improve the social legitimacy of these startups and offer government financial and logistical support for their growth. Just as importantly, the TSE has been cracking down on some of these smaller listings. they've announced that from 2030, companies that are not able to maintain a 10 billion yen market cap after five years will be delisted.

17:00Now, this might seem like a low bar. That's not a very big market cap in most countries. But in Japan, perhaps over half of firms listed on the TSE growth market don't meet even this very low bar. And so when I spoke recently to Yamachi Hiromi, the TSE's chief executive, he explained that they were trying to make an IPO the starting point for these companies, not the end goal as it historically has been. So do your mind, will that kind of intervention change anything? Are we going to be on the cusp of a new crop of unicorns in Japan? Well, there certainly is a lot of promising momentum. The number of homegrown unicorns has increased from something like one or two a decade ago to six now.

17:39There's been a sharp rise in M &A activity, a sharp rise in private equity activity. Startup acquisitions are at a record. And another tailwind that's benefited startups in Japan is AI. Japan recently registered its most valuable unicorn ever, a firm called Sakana AI, which makes large language models. But despite this promising trajectory, Japan still does need to do more. It has yet to create a Dekacorn, a startup worth more than$10 billion, unlike peer countries like Australia and Korea, which have five and six Dekacorns respectively. Japan having just one Dekacorn operating at global scale would create a motivated acquirer of promising young companies.

18:19the sorts that replete Silicon Valley. You think about Google acquiring startups created by ex-Google employees. I think Japan could draw inspiration from that model. And if it could scale up just one promising globally scaled Dekacorn, it could match some of the audacity of 20th century global firms that Japan became so famous for after the war. Ethan, thanks very much for your time. Thanks, Jason, for having me.

18:56Filing my expenses, cleaning the house, taking a parcel to the post office, I like to think I'm pretty skilled at the art of procrastination. But apparently I'm not the only one who finds fantastic excuses to delay jobs I hate. And now I'm being told that the implications could be far graver than a messy home. Procrastination is a massive problem. Benjamin Sutherland writes about science. It can reduce income. It can hurt physical health and even mental health. So how do they really measure that? What are the numbers you can put on this? There have been some pretty dramatic studies. Researchers refer to procrastination as self-regulatory failure.

19:43There was a study in 2013. They spoke to 23 ,000 Americans, had them rank themselves on a scale of one to five for procrastination. And they found that for each increase of one point on that scale, there was a$15 ,000 drop in annual earnings. So that's quite a hit. Then there's the whole issue of health. There was a fascinating study in 2023. Researchers found that those who put things off frequently also put off medical treatment and were much more likely to suffer debilitating pain. Last year, there was an analysis of 88 studies with a total of more than 63 ,000 participants in 17 countries.

20:29And they found that procrastination cut into self-esteem and was even a predictor of future depression. Okay, so it's pretty clear from what you're saying that we're studying procrastination a lot. But do we know that we actually procrastinate more than earlier generations? It appears that we are, and there's a few reasons. Number one, you have a lot of people working from home. The boss isn't looking over their shoulder. Obviously, smartphones offer an endless stream of distractions. And there's also a compounding factor with smartphones in that they tend to lead people to delay bedtime. And people who sleep less also have more problems with self-regulatory failure.

21:15Okay, so is there anything you could actually do to stop yourself procrastinating? There actually is. It's kind of surprising. One approach is a set of mental exercises that researchers call mental contrasting with implementation intentions. It involves articulating what your goal is, mentally contrasting the goal with whatever the obstacle is to getting it done and then devising a tactic to overcome it. There have been some randomized trials that found that it actually does work, at least compared to a control group that was given other types of exercises, especially with bedtime procrastination.

21:56An even more powerful way to counteract procrastination is physical exercise. In fact, there was an interesting study in China last year, they took 77 Chinese teenage boys and randomly assigned some of them exercise. And they, in fact, did end up procrastinating less at the end of the trial. There was an earlier trial also in China. This was in 2022. And they found that those who were exercising or were active physically also were less likely to procrastinate. And their explanation was that the difficulty of overcoming uncomfortable physical exertion exercise created a sense of mastery. That boosted confidence and the boosted confidence helped those students get after tasks that were unpleasant.

22:47Okay, you're talking about exercises and training we can do, which sound like prime targets for procrastination for me. Is there anything else? Are there any other habits we can change? Well, researchers have for years tried to find a link between diet, food, and procrastination. There was an interesting study in Italy in 2024. Researchers spoke with university students and determined that those who were skipping breakfast, smoking heavily, drinking heavily, were more likely to procrastinate. They hypothesized that that was because skipping breakfast deprived the students of blood sugar boost, and that led to less of an ability to be able to focus on tasks and get things done.

23:34But the problem is they weren't able to determine what was causing what. So we're not going to be prescribed any medication for procrastination anytime soon then? Yeah, probably not. In fact, there are no medications currently that target procrastination. But there was a fascinating study in America in 2021 with adults with attention deficit hyperactivity disorder. Researchers gave them a stimulant called listexafetamine, and they found that they had huge gains in cognitive executive function, which includes the ability to initiate tasks. And that didn't happen with the participants in the study who were given a placebo.

24:14So I'd say that's pretty promising, but we're still waiting for follow-up studies. So, well, it'd be good if researchers finally got a move on that. Benjamin, thank you very much. Thank you, Rosie.

24:40That's all for this episode of The Intelligence. We'll see you back here tomorrow.

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