Karuna

Cobenfy™ (formerly known as KarXT) now FDA approved for the treatment of schizophrenia in adults

Note: As of March 18, 2024, Karuna Therapeutics is a wholly owned subsidiary of Bristol Myers Squibb, acquired for $14 billion.

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Description

FDA approved for the treatment of schizophrenia in adults

PURETECH ECONOMIC INTEREST¹

PureTech retains rights to certain regulatory and commercial milestone payments related to Cobenfy™ in addition to 2% royalties on annual Cobenfy sales above $2B²

Stage of Development

FDA Approved

Note: Certain third-party trademarks are included here; PureTech does not claim any rights to any third-party trademarks. COBENFY™ (xanomeline and trospium chloride) is indicated for the treatment of schizophrenia in adults. For Important Safety Information, see U.S. Full Prescribing Information, including Patient Information on COBENFY.com. Following the acquisition of Karuna, KarXT is now under the stewardship of Bristol Myers Squibb and will be marketed as Cobenfy.
¹ Karuna Therapeutics is a wholly owned subsidiary of Bristol Myers Squibb as of March 18, 2024.
2 As of March 22, 2023, PureTech has sold its right to receive a 3% royalty from Karuna to Royalty Pharma on net sales up to $2 billion annually, after which threshold PureTech will receive 67% of the royalty payments and Royalty Pharma will receive 33%. Additionally, under its license agreement with Karuna/BMS, PureTech retains the right to receive milestone payments upon the achievement of certain regulatory approvals.

Advancing transformative medicines for people living with psychiatric and neurological conditions

Karuna Therapeutics (wholly owned subsidiary of BMS) is a clinical-stage biopharmaceutical company driven to create and deliver transformative medicines for people living with psychiatric and neurological conditions.

Program Discovery Process by the PureTech Team
- We and our collaborators, including leading schizophrenia experts, were excited about efficacy data generated in schizophrenia and Alzheimer’s disease by Eli Lilly with xanomeline, which had notable efficacy stemming from its activation of muscarinic receptors (M1 and M4) but had been held back by gastrointestinal tolerability issues. To overcome this, we invented KarXT, an oral M1/M4-preferring muscarinic agonist, by combining xanomeline (a muscarinic agonist) with trospium (a peripherally acting muscarinic antagonist that doesn’t cross the blood brain barrier). This enabled the beneficial effects of M1/M4 activation in the brain without the peripheral side effects. We conducted key human tolerability proof-of-concept studies with KarXT that allowed Karuna to advance it further in schizophrenia patients. Karuna licensed the key KarXT intellectual property from PureTech.
Milestones Achieved & Developmental Status
- In September 2024, Bristol Myers Squibb announced that Cobenfy (formerly known as KarXT) had received U.S. Food and Drug Administration approval for the treatment of schizophrenia in adults. Cobenfy is expected to be available in the U.S. in late-October.
- In March 2024, Bristol Myers Squibb (NYSE: BMY) announced the completion of its acquisition of Karuna for $330.00 per share, for a total equity value of approximately $14 billion. With the acquisition’s completion, Karuna is now a wholly owned subsidiary of BMS.
- In November 2023, Karuna announced the U.S. Food and Drug Administration (FDA) accepted its new drug application for KarXT for the treatment of schizophrenia and has granted a Prescription Drug User Fee Act (PDUFA) date of September 26, 2024.
- In November 2023, Karuna announced the Phase 3 ADEPT-2 and ADEPT-3 trials for psychosis in Alzheimer’s disease initiated in Q3 2023.
- In November 2023, Karuna announced positive results from the Phase 1b trial evaluating the effect of KarXT on 24-hour ambulatory blood pressure in adults with schizophrenia.
- In August 2023, Karuna announced the initiation of the ADEPT-3 open label extension trial in psychosis in Alzheimer’s Disease (AD).
- In March 2023, Karuna announced positive topline results from the Phase 3 EMERGENT-3 trial evaluating the efficacy, safety, and tolerability of its lead investigational therapy, KarXT (xanomeline-trospium) in adults with schizophrenia. The trial met its primary endpoint, with KarXT demonstrating a statistically significant and clinically meaningful 8.4-point reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-20.6 KarXT vs. -12.2 placebo; p<0.0001) at Week 5 (Cohen’s d effect size of 0.60). Consistent with prior trials, KarXT demonstrated an early and sustained statistically significant reduction of symptoms from Week 2 (p<0.05) through the end of the trial as assessed by PANSS total score. KarXT also demonstrated reductions in positive and negative symptoms of schizophrenia as measured by PANSS positive and PANSS negative Marder factor subscales. KarXT was generally well tolerated, with a side effect profile substantially consistent with previous trials of KarXT in schizophrenia.
- In August 2022, Karuna announced positive results from the Phase 3 EMERGENT-2 trial evaluating the efficacy, safety and tolerability of its lead investigational therapy, KarXT (xanomeline-trospium), in adults with schizophrenia. The trial met its primary endpoint, with KarXT demonstrating a statistically significant and clinically meaningful 9.6 point reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-21.2 KarXT vs. -11.6 placebo; p<0.0001) at Week 5 (Cohen’s d effect size of 0.61). KarXT also met key secondary endpoints. KarXT was generally well tolerated, with a side effect profile substantially consistent with prior trials of KarXT in schizophrenia.
Expected Milestones
- PureTech continues to hold rights to receive milestone and royalty payments upon the achievements of certain regulatory approvals and Cobenfy sales milestones. These include the up to $400 million in milestone payments under its agreement with Royalty Pharma and 2% of Cobenfy sales above $2 billion annually.²

The key innovation behind the KarXT, which was invented at PureTech, was built around two validated drugs: xanomeline, a novel muscarinic agonist, and trospium, an approved muscarinic antagonist. We were able to ameliorate the GI tolerability issues of xanomeline by pairing it with a gut-restricted muscarinic antagonist to develop a novel formulation that enabled a new approach for the potential treatment of schizophrenia and other serious psychiatric and neurological conditions, an area of major unmet need. KarXT now represents a potential first-in-class and best-in-class therapy for schizophrenia.