Karuna's Blood Pressure Trial of KarXT Successful

PureTech Founded Entity Karuna Therapeutics Announces Positive Results from Phase 1b Ambulatory Blood Pressure Monitoring Trial of KarXT in Schizophrenia

Results demonstrate KarXT was not associated with clinically meaningful increases in blood pressure in adults with schizophrenia

KarXT demonstrated a mean change from baseline to week 8 in 24-hour ambulatory systolic blood pressure of -0.59 mmHg, the primary endpoint in the trial

KarXT was generally well tolerated, with a side effect profile consistent with prior trials in the EMERGENT program evaluating KarXT in schizophrenia

PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company, noted that its Founded Entity, Karuna Therapeutics (NASDAQ: KRTX), announced positive results from its Phase 1b open-label, eight-week inpatient trial evaluating the effect of KarXT (xanomeline-trospium) on 24-hour ambulatory blood pressure in adults with schizophrenia demonstrating that KarXT was not associated with increases in blood pressure.

The primary endpoint in the trial was the change from baseline at week 8 in 24-hour average ambulatory systolic blood pressure. In the trial, KarXT demonstrated a mean change from baseline to week 8 in 24-hour ambulatory systolic blood pressure of -0.59 mmHg. The upper bound of the two-sided 95% confidence interval for the mean change from baseline to week 8 was 1.60 mmHg, thus ruling out a clinically meaningful increase in blood pressure (defined per FDA guidance as ≥3 mmHg change from baseline). Daytime and nighttime systolic blood pressure measurements showed no meaningful change and were generally consistent with the 24-hour average. Additional vital sign measures collected in the trial, including 24-hour average diastolic blood pressure and heart rate, were consistent with prior trials of KarXT in schizophrenia. Further, KarXT was generally well tolerated, with a side effect profile consistent with prior trials in the EMERGENT program.

PureTech is a founder of Karuna and co-inventor of the KarXT program. In September 2023, Karuna announced the submission of a New Drug Application to the U.S. Food and Drug Administration for KarXT for the treatment of schizophrenia. If approved, KarXT will be the third therapeutic candidate to be taken from inception at PureTech to FDA regulatory approval.

The full text of the announcement from Karuna is as follows:

Karuna Therapeutics Announces Positive Results from Phase 1b Ambulatory Blood Pressure Monitoring Trial of KarXT in Schizophrenia

Results demonstrate KarXT was not associated with clinically meaningful increases in blood pressure in adults with schizophrenia

KarXT demonstrated a mean change from baseline to week 8 in 24-hour ambulatory systolic blood pressure of -0.59 mmHg, the primary endpoint in the trial

KarXT was generally well tolerated, with a side effect profile consistent with prior trials in the EMERGENT program evaluating KarXT in schizophrenia

BOSTON -- Nov. 16, 2023 -- Karuna Therapeutics, Inc. (NASDAQ: KRTX), a biopharmaceutical company driven to discover, develop, and deliver transformative medicines for people living with psychiatric and neurological conditions, today announced positive results from its Phase 1b open-label, eight-week inpatient trial evaluating the effect of KarXT (xanomeline-trospium) on 24-hour ambulatory blood pressure in adults with schizophrenia demonstrating that KarXT was not associated with increases in blood pressure.

The primary endpoint in the trial was the change from baseline at week 8 in 24-hour average ambulatory systolic blood pressure. In the trial, KarXT demonstrated a mean change from baseline to week 8 in 24-hour ambulatory systolic blood pressure of -0.59 mmHg. The upper bound of the two-sided 95% confidence interval for the mean change from baseline to week 8 was 1.60 mmHg, thus ruling out a clinically meaningful increase in blood pressure (defined per FDA guidance as ≥3 mmHg change from baseline). Daytime and nighttime systolic blood pressure measurements showed no meaningful change and were generally consistent with the 24-hour average. Additional vital sign measures collected in the trial, including 24-hour average diastolic blood pressure and heart rate, were consistent with prior trials of KarXT in schizophrenia. Further, KarXT was generally well tolerated, with a side effect profile consistent with prior trials in the EMERGENT program.

"The data from the trial confirms our findings from the EMERGENT trials that suggested KarXT is not associated with a sustained increase in blood pressure in adults with schizophrenia," said Steve Brannan, M.D., chief medical officer of Karuna Therapeutics. "These results provide a more definitive characterization of the cardiovascular safety profile of KarXT, which substantiates the existing clinical data to date and will supplement our NDA as part of the Day 120 safety update, along with additional safety data, pending filing acceptance."

The ambulatory blood pressure monitoring trial was designed in line with FDA guidance (Assessment of Pressor Effects of Drugs, Guidance for Industry, February 2022) to provide an accurate assessment of the potential pressor effects of KarXT over a 24-hour period using ambulatory monitoring at baseline and at week 8 in adults with schizophrenia. A total of 133 adults (between the ages of 30-65 years) with a confirmed diagnosis of schizophrenia were enrolled in the trial. Trial participants received a flexible dose of KarXT two times a day (BID) for up to eight weeks. Consistent with the EMERGENT program, nearly 80% of trial participants titrated to and remained at the highest dose level of KarXT 125/30 (125mg xanomeline/30mg trospium) BID.

About KarXT

KarXT (xanomeline-trospium) is an investigational muscarinic antipsychotic in development for the treatment of schizophrenia and psychosis related to Alzheimer's disease. Through its novel mechanism of action, KarXT acts as a dual M1/M4 muscarinic acetylcholine receptor agonist in the central nervous system, which is thought to improve positive, negative, and cognitive symptoms of schizophrenia. Unlike existing treatments, KarXT does not directly block dopamine receptors, representing a potential new approach to treating schizophrenia.

About Schizophrenia

Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million people worldwide, including 2.8 million people in the U.S. It is characterized by three symptom domains: positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making). In part due to limitations with current treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships. While current treatments can be effective in managing select symptoms, approximately 30% of people do not respond to therapy, with an additional 50% experiencing only a partial improvement in symptoms or unacceptable side effects.

About Karuna Therapeutics

Karuna Therapeutics is a biopharmaceutical company driven to discover, develop, and deliver transformative medicines for people living with psychiatric and neurological conditions. At Karuna, we understand there is a need for differentiated and more effective treatments that can help patients navigate the challenges presented by serious mental illness. Utilizing our extensive knowledge of neuroscience, we are harnessing the untapped potential of the brain in pursuit of novel pathways to develop medicines that make meaningful differences in peoples' lives. For more information, please visit www.karunatx.com.