Eli Lilly bets billions on brain peptides for mental health
- Eli Lilly paid $7.8 billion for Centessa to secure its brain peptide pipeline.
- Morgan Stanley expects orexin drug sales to hit $16 billion by 2035.
- Researchers are pivoting narcolepsy treatments toward depression and addiction.
Pharmaceutical giants are buying up brain peptide developers.
On The Intelligence, global business writer Shailesh Chitnis detailed how drugmakers are turning to orexin agonists, a class of neuropeptides that function as the brain's main regulator for wakefulness. Eli Lilly spent nearly $7.8 billion to acquire Centessa Pharmaceuticals specifically for its orexin drug pipeline. The massive buyout signals a shift in how legacy pharma views neurobiology, seeking to replicate the commercial windfall seen in metabolic blockbusters.
The biology dates back to late 1990s research by Stanford scientist Dr. Emmanuel Mignot. Mignot discovered a genetic mutation in narcoleptic dogs that blocked their brains from sensing orexin signals. Subsequent human studies confirmed that patients suffering from severe narcolepsy lack these signaling molecules entirely. For decades, available treatments managed symptoms without addressing the underlying deficit.
That dynamic changed when regulators approved Takeda's ovoperextone for narcolepsy, demonstrating that synthetic peptides could target the pathway. Current narcolepsy drugs generate roughly $3 billion per year, but Wall Street foresees rapid growth. Financial models from Morgan Stanley project that orexin-based treatments will reach $16 billion annually by 2035.
The potential market extends beyond sleep medicine. Animal trials indicate that orexin pathways influence motivation and reward-seeking behavior alongside wakefulness. Chitnis noted that pharmaceutical companies plan to test orexin candidates against clinical depression, ADHD, and substance addiction.
Moving from animal models to psychiatric human trials remains a slow process. Large-scale human data for psychiatric uses is years away, and central nervous system targets carry inherent clinical risks. Even so, traditional psychiatric drugs face high failure rates, pushing major firms to back novel mechanisms.
The search for neurology's next blockbuster class is underway.
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Wake-up haul: an Ozempic moment for the brain • Aug 19
- Shailesh Chitnis highlights orexin agonists as the pharmaceutical industry's next major class of drugs, mimicking brain peptides that regulate wakefulness. Takeda's recently approved drug ovoperextone targets narcolepsy, which currently affects between 1 in 1,000 and 1 in 2,000 people.
- Stanford researcher Dr. Emmanuel Mignot discovered the genetic basis of narcolepsy in the late 1990s by studying Dobermans and Labradors. His work revealed that a genetic mutation preventing dogs from responding to orexin caused the sleep disorder.
- Shailesh Chitnis notes that while currently targeted at narcolepsy, orexin regulates reward-seeking behavior and motivation in animal trials. This suggests future applications for treating depression, ADHD, and addiction, though human trials for these conditions remain in early stages.
Also discussed on this episode: (9)
VC (1)
- Investment in orexin drugs is surging, exemplified by Eli Lilly's $7.8 billion acquisition of Centessa Pharmaceuticals. Morgan Stanley projects the global market for these wakefulness-regulating treatments will reach $16 billion annually by 2035, up from the current $3 billion.
Startups (3)
- Japan struggles to produce high-value startups, claiming only six of the world's 1,400 unicorns. Ethan Wu points to a severe shortage of late-stage venture capital as a primary barrier to scaling these domestic businesses globally.
- Japanese startups frequently rush to public listings to secure liquidity rather than pursuing mergers. To curb this trend, the Tokyo Stock Exchange will delist companies that fail to maintain a 10 billion yen market cap after five years starting in 2030.
- Japan lacks a single decacorn, whereas regional peers South Korea and Australia boast six and five respectively. Ethan Wu argues that a homegrown ten-billion-dollar firm is vital to act as an active acquirer and anchor for the broader startup ecosystem.
Society (1)
- Cultural aversion severely limits Japan's entrepreneurial pipeline. Ethan Wu highlights a Global Entrepreneurship Monitor survey showing that only 24% of Japanese view entrepreneurship as a desirable career, compared to a global average of 67%.
Psychology (4)
- Procrastination functions as a self-regulatory failure with severe real-world costs. Benjamin Sutherland notes that a 2013 study linked a one-point increase on a five-point procrastination scale to a $15,000 drop in annual household earnings.
- Beyond financial damage, chronic procrastination correlates with poor health and depression. A meta-analysis of 88 studies involving over 63,000 participants across 17 countries confirmed that delaying tasks diminishes self-esteem and directly predicts future depression.
- Cognitive and physical strategies can reduce procrastination. Mental contrasting with implementation intentions helps users overcome task barriers, while physical exercise builds a sense of mastery that boosts confidence to tackle unpleasant jobs.
- Studies show lifestyle and medical links to task avoidance. A 2024 Italian study tied skipping breakfast to higher procrastination, while a 2021 US study on ADHD patients found the stimulant lisdexamfetamine significantly improved executive function and task initiation.