Phase 1b Study of DCR-AUD in Healthy Volunteers

Inclusion Criteria

• 21 to 65 years, inclusive, at the time of signing informed consent.
• Overtly healthy volunteers, as determined by medical evaluation including medical history, physical examination, and laboratory testing.
• No diagnosis of AUD within the preceding 12 months per Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
• Social drinkers who consume, on average, 5 to 20 drinks per week for men or 5 to 14 drinks per week for women over the 4 weeks prior to Screening, and not more than 8 drinks in a single day.
• No evidence of overt or sub-clinical hepatic pathology, as manifest by serologic tests demonstrating hepatic inflammation or compromised hepatic synthetic function (i.e., AST, ALT, GGT, total bilirubin 7%. Asthma requiring hospital admission within the preceding 12 months. NOTE: Persons with clinically stable asthma who have not been hospitalized in the prior year and are treated only with orally inhaled medications are not excluded. d. Currently poorly controlled endocrine conditions, except for hypothyroidism that is stable (no treatment change in prior 6 months). e. Significant infection or known systemic inflammatory process ongoing at Screening.

f. History of chronic or recurrent UTI, or UTI within 1 month prior to Screening.

• History of malignancy within the preceding 5 years requiring treatment, with the exception of excised low grade basal cell skin neoplasms. 9. History of any concomitant medical condition for which alcohol consumption is prohibited or advised against by the participant's physician or health care provider.
• SARS-CoV-2 infection in the 14 days prior to randomization. 11. Clinically significant illness within the 7 days prior to the first administration of study intervention. History of multiple drug allergies or a history of allergic reaction to an oligonucleotide based therapy.
• Use of prescription medications (except for hormonal replacement/contraceptive medication for women and inhaled medication for treatment of clinically stable asthma) within 14 days or 5 half-lives (whichever is longer) prior to administration of study intervention. Participants being treated for hypothyroid disease must be on stable treatment (no treatment changes in the preceding 6 months). 14. Receipt of any vaccine (including COVID-19) within 14 days prior to the first administration of study intervention. 15. Regular use of OTC medications, including NSAID (periodic or occasional NSAID use to control temporary pain is not exclusionary). 16. Previously participated in Dicerna Study DCR-AUD-101. 17. Has received an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to dosing or is in follow-up of another clinical study prior to initial dosing with the study intervention. 18. Clinically significant abnormalities in vital signs at Screening: pulse rate ( 90 bpm), respiratory rate, or temperature. 19. Clinically significant abnormalities in 12-lead ECG at Screening or predose on Day 1, including QTcF > 470 msec in females and > 450 msec in males. 20. Positive urine drug test at Screening or Day -1. Tests positive for cannabis are not exclusionary. 21. Seropositive for antibodies to HIV, HBV, or HCV at Screening (historical testing may be used if performed within the 3 months prior to screening). NOTE: In participants with previous treatment for hepatitis C with direct-acting HCV medication and seropositivity for HCV, or in participants with prior infection and spontaneous resolution, HCV RNA must be undetectable (at least 2 negative HCV RNA tests at least 12 weeks apart), and the HCV infection must have been resolved or cured > 3 years prior to initial dosing with the investigational medication. 22. Safety laboratory test result at Screening considered clinically unacceptable for study participation by the Investigator. 23. History of intolerance to SC injection(s) or significant abdominal scarring that could potentially hinder study intervention