Karuna Therapeutics and Bristol Myers Squibb are winners of the 2025 Gizmodo Science Fair for their research and development of Cobenfy (xanomeline-trospium), the first truly novel medication for schizophrenia seen in 50 years.
The question
Can we find another way to tackle schizophrenia and other psychiatric disorders and do it without the heavy side effects of modern drugs?
The results
Last fall, the Food and Drug Administration approved Cobenfy (a twice-daily pill) for schizophrenia. In the pivotal clinical trials that secured its approval, people on the drug experienced a significant reduction in their symptoms compared to placebo, including “positive” symptoms like hallucinations. It was also safely tolerated, with fewer people experiencing the adverse effects common to other antipsychotics, such as weight gain.
Why they did it
For Andrew Miller, lead inventor of Cobenfy and founder of Karuna Therapeutics, Cobenfy’s approval was the culmination of an effort that first began over 15 years ago (Bristol Myers Squibb completed its acquisition of Karuna in 2024).
Nearly every schizophrenia drug today works by targeting the neurotransmitter dopamine in our brain (some schizophrenia symptoms are linked to too much dopamine in certain brain regions, while others are linked to insufficient dopamine elsewhere). But Cobenfy takes a different approach.
The first half of Cobenfy, xanomeline, targets the neurotransmitter acetylcholine through activating two specific receptors in the brain (muscarinic acetylcholine receptors 1 and 3). Earlier research in the 1990s suggested that xanomeline could potentially alleviate symptoms common to schizophrenia and other forms of psychosis. Unfortunately, those same studies also showed the drug could cause serious adverse side effects by activating these receptors elsewhere in the body, particularly the gut.
“Fifteen years ago, I started talking to researchers in schizophrenia, asking questions like, ‘Where’s the emerging science? What’s interesting?’ And one of the ideas that I kept coming back to was this muscarinic idea. But there was this challenge. There was some evidence that suggests it works, but we can’t overcome these side effect considerations,” Miller told Gizmodo.
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