Karuna Therapeutics, Inc. was a clinical-stage biopharmaceutical company focused on developing transformative medicines for neuropsychiatric disorders. The company was acquired by Bristol-Myers Squibb in March 2024.
Founded in 2009 as Karuna Pharmaceuticals, the company developed KarXT (xanomeline-trospium), a novel muscarinic receptor agonist with potential applications in schizophrenia and psychosis associated with Alzheimer's disease[1].
Karuna was founded based on research from Yale University and the University of Minnesota on muscarinic receptor biology. The company's founding insight was that muscarinic receptor activation could treat psychosis without the dopamine-blocking side effects of traditional antipsychotics.
The acquisition represented one of the largest CNS deals in pharmaceutical history, validating Karuna's innovative approach to muscarinic receptor targeting.
KarXT is a novel muscarinic receptor agonist that selectively targets M1 and M4 muscarinic acetylcholine receptors while avoiding D2 dopamine receptor blockade. This represents a fundamentally different mechanism from current antipsychotics[3]:
The cholinergic hypothesis of psychosis suggests that:
| Trial | Indication | Stage | Results |
|---|---|---|---|
| EMERGENT-1 | Schizophrenia | Phase 2 | Positive (2022) |
| EMERGENT-2 | Schizophrenia | Phase 3 | Positive (2023) |
| EMERGENT-3 | Schizophrenia | Phase 3 | Positive (2023) |
| EMERGENT-4 | Schizophrenia | Phase 3 | Positive (2023) |
| ADEPT-1 | Alzheimer's psychosis | Phase 3 | Ongoing |
| ADEPT-2 | Alzheimer's psychosis | Phase 3 | Ongoing |
| ARISE | Schizophrenia (adjunct) | Phase 3 | Positive (2024) |
Acetylcholine acts on two families of receptors:
There are five muscarinic receptor subtypes (M1-M5):
KarXT uses a clever combination:
The muscarinic receptor approach represents a paradigm shift in psychosis treatment[5]:
Mechanism distinct from D2 blockade
May benefit patients refractory to current treatments
COBENFY
Karuna Therapeutics. Company Archive. ↩︎
Karuna Acquisition Analysis. Wall Street Journal. ↩︎
KarXT Mechanism. Nature Medicine. ↩︎
COBENFY FDA Approval. FDA Press Release. ↩︎
Muscarinic Agonists in Psychosis. American Journal of Psychiatry. 2022. ↩︎