An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (EMERGENT-5)

Inclusion Criteria:

1. Subject is aged 18 to 65 years at screening.

2. Subject is capable of providing informed consent.

3. A signed informed consent form (ICF) must be provided before any studyassessments are performed.

4. Subject must be fluent in (oral and written) the language of the ICGF toconsent.

5. Subject has a primary diagnosis of schizophrenia established by a comprehensivepsychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013)criteria and confirmed by Mini International Neuropsychiatric Interview forSchizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.

6. Subject has not required psychiatric hospitalization, acute crisis intervention, orother increase in level of care due to symptom exacerbation within 8 weeks ofscreening and is psychiatrically stable in the opinion of the investigator.

7. PANSS total score ≤ 80 at screening and Baseline Visit B (Day 0).

8. Clinical Global Impression - Severity (CGI-S) score of ≤ 4 at screening and BaselineVisit B (Day 0).

9. At the time of screening, or at any time within the 30 days prior to screening, thesubject must have received an oral antipsychotic medication daily at a dose andfrequency consistent with the drug label.

10. In the opinion of the investigator, it is clinically appropriate for the subject todiscontinue current antipsychotic therapy and initiate experimental treatment withKarXT.

11. Subject is willing and able, in the opinion of the investigator, to discontinue allantipsychotic medications prior to baseline visit.

12. Subject has an identified reliable informant willing to be able to address somequestions related to certain study visits, if needed. An informant may not benecessary if the subject has been the patient of the investigator for ≥1 year.

13. At Day 0, subject will have been off lithium therapy for at least 2 weeks and musthave discontinued all oral antipsychotic medications.

14. Subjects taking a long-acting injectable antipsychotic could not have received adose of medication for at least 12 weeks (24 weeks for paliperidone palmitate)before Day 0.

15. Body mass index must be ≥ 18 and ≤ 40 kg/m2.

16. Subject resides in a stable living situation and is anticipated to remain in astable living situation for the duration of study enrollment, in the opinion of theinvestigator.

17. Women of childbearing potential or men with sexual partners of childbearingpotential must be willing and able to use at least 1 highly effective method ofcontraception during the study and for at least 30 days after the last dose ofKarXT. Sperm donation is not allowed for 30 days after the final dose of KarXT.

Exclusion Criteria:

1. Any primary DSM-5 disorder other than schizophrenia within 12 months beforescreening (confirmed using MINI version 7.0.2 at screening).

2. Subject has a history of moderate to severe alcohol use disorder or a substance (other than nicotine or caffeine) use disorder within the past 12 months or apositive urine drug screen (UDS) for a substance other than cannabis at screening orbaseline.

3. History or presence of clinically significant cardiovascular, pulmonary, hepatic,renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,neurologic, or oncologic disease or any other condition that, in the opinion of theinvestigator, would jeopardize the safety of the subject or the validity of thestudy results

4. Subject has human immunodeficiency virus (HIV), cirrhosis, biliary ductabnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections basedon either medical history or liver function test results.

5. History or high risk of urinary retention, gastric retention, or narrow-angleglaucoma

6. History of irritable bowel syndrome (with or without constipation) or seriousconstipation requiring treatment within the last 6 months

7. Risk for suicidal behavior during the study as determined by the investigator'sclinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).

8. Clinically significant abnormal finding from the physical examination, medicalhistory, ECG, or clinical laboratory results at screening.

9. Subjects cannot currently (within 5 half-lives before Day 0) be receiving monoamineoxidase inhibitors, anticonvulsants, tricyclic antidepressants, centrally activeanticholinergics, or any other psychoactive medications other than dailyantipsychotic maintenance therapy. As-needed anxiolytics and/or sleep aids arepermitted. Selective serotonin reuptake inhibitors and serotonin-norepinephrinereuptake inhibitors taken at stable dose may be permitted.

10. Subject has a history of treatment resistance to schizophrenia medications definedas failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeksat an adequate dose per the label) within the past 12 months or having receivedclozapine within the past 3 years

11. Pregnant, lactating, or less than 3 months postpartum.

12. If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable forenrollment in the study or subject has any finding that, in the view of theinvestigator (and/or Sponsor), may compromise the safety of the subject or affecthis/her ability to adhere to the protocol visit schedule or fulfill visitrequirements.

13. Subjects has tested positive for coronavirus disease 2019 (COVID-19) within 2 weeksof screening.

14. Subject has extreme concerns relating to global pandemics, such as COVID-19, thatpreclude study participation.

15. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative)within the 6 months before screening.

16. Subject has prior exposure to KarXT.

17. Risk of violent or destructive behavior.

18. Current involuntary hospitalization or incarceration.