"A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder"

Inclusion Criteria:

Participants must meet all the following criteria to be included in the trial:

• Aged 18 to 85 years inclusive, at Screening

• Participant has a diagnosis of MDD (single or recurrent episode as defined by DSM-5TR [if single episode, duration of ≥4 weeks and ≤24 months] and established as perevaluation by the Investigator. The first MDD episode must have occurred prior toage 60.

• Depression is of moderate to severe degree at Screening, independently confirmed byadditional clinical assessments

• Participant has been on a stable dose of a single antidepressant medication at anadequate dose (label specified) for an adequate duration in the last 4 weeks priorto Screening and has had an inadequate response (less than 50% improvement), asjudged by the Investigator and clinical interviews.

• Participant has a body mass index (BMI) of 40 kg/m2 or less (BMI ≤ 40 kg/m2),inclusive, at Screening.

• Participant is able to refrain from nicotine use during the dosing session (up to 8hours)

• Registered with a healthcare professional who can confirm the diagnosis and previoustreatments received by the participant.

• Participants capable of producing sperm must use a condom during the trial and for 12 weeks after their final dose of trial medication, if their partner is a person ofchildbearing potential. In addition, their partner of childbearing potential mustuse a highly effective method of contraception (i.e., failure rate less than 1% whenused consistently and correctly) from first dosing until 12 weeks following finaldosing.

• Participants of childbearing potential who have a partner capable of producing spermmust agree to use a highly effective method of contraception (i.e., failure rateless than 1% when used consistently and correctly) in combination with the use of acondom plus spermicide during the trial and for 12 weeks after their final dose oftrial medication. Such participants must have a negative pregnancy test at Screeningand Day -1 prior to dosing.

• Female participants who were capable of producing eggs (ova) must be postmenopausalor permanently sterile following hysterectomy, bilateral salpingectomy, andbilateral oophorectomy. Postmenopausal is defined as spontaneous amenorrhea for atleast 12 months, and a serum follicle-stimulating hormone level in the menopausalrange, unless the participant is taking hormone replacement therapy or is usinghormonal contraception.

• Participant has provided written informed consent, which includes compliance withthe requirements and restrictions listed in the informed consent form.

Exclusion Criteria:

Participants with any of the following characteristics/conditions will be excluded from trial participation:

• Current or previously diagnosed schizophrenia spectrum or other psychotic disorders,including schizophrenia, schizoaffective disorder, schizotypal disorder,schizophreniform disorder, brief psychotic disorder, attention deficit hyperactivitydisorder, current or previous history of bipolar disorder, or current borderlinepersonality disorder.

• Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1 (first degree relatives).

• Significant suicide risk within the past 6 months, during the Screening Period, orat Baseline; or (b) suicidal behaviors within 12 months of Screening; or (c)clinical assessment of significant suicidal risk during clinical interview; or (d)non-suicidal self-injury within 12 months of Screening.

• Current or previous diagnosis of treatment-resistant MDD, defined as failure torespond to 2 or more antidepressant treatments of 2 different classes given at anadequate dose for an adequate duration as judged by the Investigator and clinicalinterview.

• Has had electroconvulsive treatment, transcranial magnetic stimulation, deep brainstimulation, or vagal nerve stimulation for any episode of MDD in the last 6 months.

• Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressant,mirtazapine, trazodone, moclobemide, buspirone, ketamine or S-ketamine, or anantipsychotic or mood stabilizer for MDD.

• Participant report of (or if available in medical record) exposure to psilocin, or 5-HT2a receptor agonists, or any other psychedelics, such as ayahuasca, mescaline,lysergic acid diethylamide, peyote, or 3,4-methylenedioxymethamphetamine, more than 

• Participant is able to refrain from nicotine use during the dosing session (up to 8
hours)
 

• Registered with a healthcare professional who can confirm the diagnosis and previous
treatments received by the participant.
 

• Participants capable of producing sperm must use a condom during the trial and for
 12 weeks after their final dose of trial medication, if their partner is a person of
childbearing potential. In addition, their partner of childbearing potential must
use a highly effective method of contraception (i.e., failure rate less than 1% when
used consistently and correctly) from first dosing until 12 weeks following final
dosing.
 

• Participants of childbearing potential who have a partner capable of producing sperm
must agree to use a highly effective method of contraception (i.e., failure rate
less than 1% when used consistently and correctly) in combination with the use of a
condom plus spermicide during the trial and for 12 weeks after their final dose of
trial medication. Such participants must have a negative pregnancy test at Screening
and Day -1 prior to dosing.
 

• Female participants who were capable of producing eggs (ova) must be postmenopausal
or permanently sterile following hysterectomy, bilateral salpingectomy, and
bilateral oophorectomy. Postmenopausal is defined as spontaneous amenorrhea for at
least 12 months, and a serum follicle-stimulating hormone level in the menopausal
range, unless the participant is taking hormone replacement therapy or is using
hormonal contraception.
 

• Participant has provided written informed consent, which includes compliance with
the requirements and restrictions listed in the informed consent form.
 
 Exclusion Criteria:
 
 Participants with any of the following characteristics/conditions will be excluded from
 trial participation:
 

• Current or previously diagnosed schizophrenia spectrum or other psychotic disorders,
including schizophrenia, schizoaffective disorder, schizotypal disorder,
schizophreniform disorder, brief psychotic disorder, attention deficit hyperactivity
disorder, current or previous history of bipolar disorder, or current borderline
personality disorder.
 

• Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type
 1 (first degree relatives).
 

• Significant suicide risk within the past 6 months, during the Screening Period, or
at Baseline; or (b) suicidal behaviors within 12 months of Screening; or (c)
clinical assessment of significant suicidal risk during clinical interview; or (d)
non-suicidal self-injury within 12 months of Screening.
 

• Current or previous diagnosis of treatment-resistant MDD, defined as failure to
respond to 2 or more antidepressant treatments of 2 different classes given at an
adequate dose for an adequate duration as judged by the Investigator and clinical
interview.
 

• Has had electroconvulsive treatment, transcranial magnetic stimulation, deep brain
stimulation, or vagal nerve stimulation for any episode of MDD in the last 6 months.
 

• Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressant,
mirtazapine, trazodone, moclobemide, buspirone, ketamine or S-ketamine, or an
antipsychotic or mood stabilizer for MDD.
 

• Participant report of (or if available in medical record) exposure to psilocin, or
 5-HT2a receptor agonists, or any other psychedelics, such as ayahuasca, mescaline,
lysergic acid diethylamide, peyote, or 3,4-methylenedioxymethamphetamine, more than
 4 times over the participant's lifetime or any psychedelic use within 12 monthsprior to Screening.

• Clinically relevant history of abnormal physical health interfering with the trialas determined by medical history and physical examinations obtained during Screeningas judged by the Investigator (including but not limited to, neurological,cardiovascular, respiratory, gastrointestinal [including dyspepsia orgastroesophageal reflux disease], hepatic, or renal disorder).

• Participants with renal insufficiency.

• Has hypothyroidism or hyperthyroidism, unless controlled on appropriate medicationwith no change in dosage for at least 12 weeks prior to Screening.

• Current diagnosis of uncontrolled hypertension or an arrhythmia, or clinicallyrelevant abnormal results for heart rate or blood pressure

• History or clinical evidence of any disease and/or existence of any surgical ormedical condition which might interfere with the absorption, distribution,metabolism, or excretion of the trial medication.

• Participant has a presence or relevant history of organic brain disorders (e.g.,epilepsy, seizure, intracranial hypertension, intracranial bleed and aneurysmaldisease, brain tumor or other medical conditions associated with seizures orconvulsions).

• Known sensitivity to psilocin and/or any excipients present in the formulation.

• Participant is taking or has taken OTC doses of 5 hydroxytryptophan or St John'sWort within 45 days prior to trial medication administration.

• Strenuous exercise within 48 hours prior to each clinic visit.

• The participant has participated in a clinical trial and has received a medicationor a new chemical entity within 12 weeks prior to dosing of current trialmedication.

• Participants capable of producing sperm who will not abstain from sperm donationbetween first dosing and 12 weeks after final dosing.

• Participants of childbearing potential who are pregnant, breastfeeding, planning toconceive or unwilling to abstain from egg (ova) donation between first dosing and 12weeks after final dosing.

• History of serotonin syndrome.

• Unwilling to consent to audio and video recording of psychological support anddosing sessions.