OLANI PK/Safety Study in Healthy Volunteers

Naltrexone (NTX) is a nonspecific pure opioid antagonist with a high affinity for the
µ-opioid receptor. It blocks the effects of opioids by competitive binding at opiate
receptors. NTX is used primarily in the management of opiate and alcohol dependence. It is
available in the United States (US) as 2 formulations; a once daily oral formulation (Revia)
and a once monthly intramuscular injection (Vivitrol). While NTX is a potent antagonist and
efficiently blocks the effects of exogenous opiates such as heroin, the success of NTX for
the treatment of opiate dependence has been limited by poor patient compliance. Therefore,
the development of a sustained release NTX formulation (in excess of 1 month) would be of
great benefit for the treatment of opioid use disorder.

Inclusion Criteria:

- Men or women between the ages of 18 and 55 years old (inclusive)

- Without DSM 5 (The Diagnostic and Statistical Manual of Mental Disorders, Fifth
Edition ) - Substance Related Disorders classification; in sustained remission is not
exclusionary

- Able and willing to comply with the requirements of the protocol

- Able and willing to provide written informed consent

- Willing to undergo a minor surgical procedure under local anesthetic to allow for
investigational drug administration in the subcutaneous tissue

- BMI inclusive of 18.5 to 30.0

- Have an initial weight between 45.3 and 81.6 kilograms (inclusive)

Exclusion Criteria:

- Positive urine drug screen (UDS) at screening for illicit substances.

- Is currently on naltrexone medication.

- Has had a naltrexone implant in the past 24 months.

- Has received treatment with an extended naltrexone product (e.g. Vivitrol) in the past
12 months.

- Has a condition which requires treatment with opioid based medication.

- Has a known hypersensitivity to naltrexone.

- Has a known hypersensitivity to poly-lactic based materials e.g. biodegradable
sutures, surgical implants or previous biodegradable implants.

- Has a known hypersensitivity to local anesthesia.

- Is prone to skin rashes, irritation or has a skin condition such as recurrent eczema
that is likely to impact the implant site area, or as determined by the evaluating
physician.

- Demonstrates any abnormal skin tissue in the proposed implantation area.

- Is pregnant or planning to be. Women need to have negative blood pregnancy test at
screening. Women need to agree to practice dual contraceptives.

- Participant is breastfeeding or planning to be.

- Has a current significant neurological (including cognitive and psychiatric
disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary,
hematological or metabolic disease unless currently controlled and stable with
protocol-allowed medication 30 days prior to proposed investigational product
administration.

- Any clinically important abnormal finding as determined by medical history, physical
examination, ECG or clinical laboratory tests.

- Any additional condition(s) that in the investigator's opinion would prohibit the
participant from completing the study or would not be in the best interest of the
participant.

- Alanine aminotransferase (ALT) or aspartate transaminase (AST) > 3 times the upper end
of the laboratory normal range.

- Any methadone use 14 days prior to screening, and up to Study Day 0.

- Current DSM-5 diagnosis of schizophrenia, bipolar, anxiety, or depressive disorder,
confirmed by the MINI diagnostic interview assessment, or currently treated with
medications for anxiety or depression. Past history (in remission DSM-5
classification) of anxiety or depression is not exclusionary.

- Any elevated risk for suicide measured using the Columbia Suicide Severity Rating
Scale, endorsing any of the items in the past month (C-SSRS, Lifetime)

- Is participating or intending to participate in any other clinical trial during the
duration of this study.