A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms

Inclusion Criteria:

   - Patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
   diagnosis of schizophrenia or schizoaffective disorder as confirmed by the Mini
   International Neuropsychiatric Interview (MINI)

   - Part B only: Stable treatment with a dopamine/serotonin (D2/5HT2A) antagonist or pure
   D2 antagonist(s), or a D2 partial agonist for a minimum of 6 months and receiving no
   more than two antipsychotics

   - Medically stable during the 3 months prior to study entry

   - Participant is an outpatient with no psychiatric hospitalizations within the prior 6
   months

   - PANSS negative symptom factor score of 18 or higher

   - The following rating on items of the PANSS: (a) less than 5 on G8 (uncooperativeness),
   P1 (delusions), P3 (hallucinations), P4 (excitement/hyperactivity), and P6
   (suspiciousness/persecution); (b) less than 4 on P7 (hostility), and G14 (poor impulse
   control)

   - Has an informant who is considered reliable by the Investigator

   - Body mass index (BMI) between 18-40 kg/m2 inclusive

   - Female participants are eligible to participate if not pregnant, not breastfeeding and
   agree to remain abstinent or use acceptable contraceptive methods during the treatment
   period and for at least 28 days after the last dose of study drug

Exclusion Criteria:

   - Moderate to severe substance use disorder within six months of study entry (excluding
   nicotine or caffeine) as defined by DSM-5

   - Extrapyramidal symptom rating scale (ESRS-A CGI) subscore greater than or equal to 3

   - Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)

   - PANSS item G6 (depression) greater than or equal to 5

   - Significant risk of suicide or harming him- or herself or others according to the
   Investigator's judgment

   - A prior or current general medical condition that might be impairing cognition or
   other psychiatric functioning

   - Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C
   (HCV), or HIV-1 and HIV-2. HCV antibody positive participants are eligible if HCV RNA
   is negative

   - Tardive dyskinesia that is moderate to severe or requires treatment

   - History of neuroleptic malignant syndrome

   - Average triplicate Fridericia's Correction Formula (QTcF) interval greater than 450
   milliseconds (msec) for males and 470 msec for females or other clinically significant
   abnormality on screening electrocardiogram (ECG) based on centralized reading

   - Clinically significant abnormalities in laboratory safety test results

   - Significant or unstable physical condition that in the investigator's judgment might
   require a change in medication or hospitalization during the course of the study

   - On more than one antidepressant, or if on one antidepressant, a change in dose within
   28 days prior to screening

   - History of clozapine treatment

   - History of treatment with electroconvulsive therapy (ECT)

   - Concomitant use of prohibited medications

   - Positive urine drug screen for amphetamines, methamphetamines, opiates,
   buprenomorphine, methadone, cannabinoids, cocaine, and barbiturates

   - Receipt of an investigational drug within 28 days or five times the half-life of the
   investigational drug (whichever is longer) before the first study drug administration

   - Donation of blood over 400 mL within 3 months prior to screening

   - Diagnosis of COVID-19 infection (confirmed or presumptive) 4 weeks prior to screening
   or during screening. Participants can be re-screened after 4 weeks of full recovery in
   addition to Investigator and/or institutional approval to enroll