A study to investigate the safety, tolerability, blood concentrations and effects of multiple doses of DNL104 in healthy volunteers.

1. Healthy men or women between 18 and 55 years of age at screening (inclusive);

2. Subjects must be willing and able to give written informed consent, and must sign an ethics-committee-approved Informed Consent Form prior to any study-related procedures being performed;

3. Body mass index between 19 to 32 kg/m2 (inclusive) and a weight of at least 50 kg;

4. For males: When engaging in sexual activity with a woman of childbearing potential, both the subject and his female partner must use highly effective contraception, consisting of 2 forms of birth control (1 of which must be a male barrier method such as latex or polyurethane condoms) from screening, throughout the clinical study period, and for 90 days after the final study drug administration;

5. For males: The subject must not donate sperm from screening, throughout the clinical study period, and for 90 days after the final study drug administration;

6. For females: The subject must have been surgically sterilized (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; proper documentation required) at least 6 months before screening, or be postmenopausal (defined as 24 months without menses before screening, with an estradiol level of < 200 pmol/L and a follicle-stimulating hormone level of > 40 IU/L at screening);

7. Able to communicate with the investigator and study staff;

8. Willing and able to comply with the requirements of the study, scheduled visits, laboratory tests, and other study procedures;

9. Agrees to abide by study restrictions and agrees to remain in the study unit for the confinement period.

1. History of clinically significant neurologic, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders;

2. Current significant medical or psychiatric condition, including suicidal ideation in the last 6 months (as assessed by the C-SSRS) or a lifetime suicide attempt;

3. Clinical laboratory test values outside the normal range at screening or baseline unless assessed by the investigator as clinically non-significant values;

4. Supine systolic blood pressure <90 or >140 mmHg, supine diastolic blood pressure <50 or >90 mmHg, pulse rate <40 or >110 bpm, or elevated body temperature at screening or baseline;

5. History of serious adverse reaction or serious hypersensitivity to any drug;

6. Evidence of clinically significant hepatic or renal impairment including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 x the upper limit of normal (ULN), or bilirubin >1.2 x ULN, or GGT >2.5 x ULN, or creatinine clearance (determined by the MDRD study equation) of <70 mL/min/1.73 m2;

7. History of seizures;

8. History or presence of an abnormal ECG, including, but not limited to, complete left bundle branch block, second- or third-degree heart block, evidence of prior myocardial infarction, or any other abnormality that is clinically significant in the investigator’s opinion or precludes accurate interpretation and calculations of cardiac intervals (e.g., QT, QRS);

9. A QTcF value >450 msec or QRS >120 msec demonstrated in at least two ECGs recorded more than 30 min apart;

10. Hemoglobin level <7.5 mmol/L;

11. Any blood donation or other loss of blood greater than 500 mL within 3 months of screening or plasma donation within 2 weeks of screening;

12. Participation in any other investigational drug study within 90 days of first study drug administration, or previous participation in a study with DNL104.

13. Use of any prescription drug within 7 days or 5 half-lives (whichever is longer) of the first dose administration and anticipated use through the follow-up 1 visit;

14. Use of any over-the-counter medication (including vitamin/mineral supplements, and herbal medicines such as St. John's Wort) within 7 days of the first dose administration and anticipated use through the follow-up 1 visit;

15. Any surgical or medical condition possibly affecting drug absorption (e.g., gastrectomy);

16. Poor peripheral venous access;

17. Alcohol, caffeine, or grapefruit consumption within 48 h before dosing;

18. Average daily caffeine intake greater than 450 mg/ day (equivalent to 4 cups per day);

19. History of alcoholism, drug abuse, or drug addiction in the last 2 years;

20. Positive drug or alcohol test at screening or upon admission to the unit;

21. Use of tobacco or nicotine products within the previous month before the first dose administration;

22. Positive serology for HIV, HBV, or HCV, by HIV1 and HIV2 antibodies, Hepatitis B antigen or Hepatitis C antibodies, respectively;

23. Subjects who are part of the clinical staff personnel or family members of the clinical site staff;

24. Any other issue which, in the opinion of the Investigator, will make the subject ineligible for study participation;

25. Subjects who are unwilling to agree to any food restrictions that may be required.