A Study Investigating the Safety, Absorption, Elimination, and the Effect on the Immune System of ACI-19764 in Healthy Participants and in Participants With Cardiovascular Risk Factors

1. Known hypersensitivity to any excipient of the ACI-19764 formulations.

2. Known clinically relevant hypersensitivity or allergy to any therapeutic treatment (including non-steroidal anti-inflammatory drugs \[NSAIDs\], or nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 \[NLRP3\] inhibitors), vaccines, cosmetics, natural rubber or latex and/or food.

3. Clinically relevant findings on the physical examination at screening or on Day -1.

4. Clinically relevant findings in clinical laboratory tests

5. Clinically relevant history or presence of rhythm disorders, congestive heart failure, or structural heart disease.

6. History or presence of clinically relevant surgical intervention which, in the opinion of the investigator, could potentially interfere with the safety/tolerability and/or absorption, distribution, metabolism, and excretion (ADME) of the study treatment.

7. History or presence of acute, ongoing, recurrent, or chronic clinically relevant diseases which, in the opinion of the investigator, could potentially interfere with the assessment of safety/tolerability and/or ADME of the study treatment. For Part C: obesity, well-controlled type 2 diabetes, well-controlled hypertension, hypercholesterolemia, and osteoarthritis are acceptable co-morbidities.

8. For Part C: occurrence of diabetic ketoacidosis within the last 3 months

9. History or current acute or chronic pulmonary pathology including but not limited to chronic obstructive pulmonary disease (COPD), asthma, and recurrent lung infections.

10. Lifetime history of suicide attempt (including active attempt, interrupted attempt or aborted attempt) or suicidal ideation in the past 6 months according to the C-SSRS at screening (Parts B and C only).

11. History of cancer within the past 5 years other than treated squamous cell carcinoma, basal cell carcinoma, and melanoma in situ, or in-situ prostate cancer, in-situ cervix carcinoma, or in-situ breast cancer which have been fully removed and are considered cured.

12. Previous unexplained history of recurrent pre-syncope or syncope with no clear provoking features or syncope in the context of medical investigations that is likely to complicate interpretation of the safety of the drug in the opinion of the Investigator.

13. Veins unsuitable for intravenous (i.v.) puncture on both arms.

14. Participation in a clinical study involving study treatment administration within 3 months (or within 5 half-lives before screening, whichever is longer) prior to (the first) study treatment administration or in more than 3 clinical studies within 1 year prior to (the first) study treatment administration.

15. History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.

16. Consumption of \>14 units of alcohol per week (females) or \>21 units per week (males).

17. Excessive caffeine consumption.

18. Nicotine consumption from 3 months prior to (first) study treatment administration, checked at screening and on Day -1.

19. Loss (including donation) of 450 mL or more of blood or blood products within 2 months prior to (the first) study treatment administration.

20. Positive results from serum/urine drug or alcohol screen test at screening or on Day -1.

21. Positive hepatitis B and/or C serology results, except for vaccinated participants or those with past but resolved hepatitis, at screening.

22. Positive human immunodeficiency virus (HIV) serology results at screening.

23. Any circumstances or conditions which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

24. Legal incapacity or limited legal capacity at screening.

25. Treatment or intended treatment with any prescribed medications within 2 weeks prior to (first) study treatment administration, except for contraceptives (including hormonal contraceptive devices) in female participants (Part B and C only), and/or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 1 week prior to (first) study treatment administration. Analgesia with paracetamol is acceptable (but not NSAIDs or aspirin \>75 mg per day), unless for the short-term treatment of post lumbar puncture (LP) headache. For Part C: prescribed and OTC (including vitamins and minerals) are permitted (apart from exceptions listed below) provided they have been on a stable dose in the 3 months prior to screening.

26. Any immunosuppressive therapies within 2 months or 5 half-lives (whichever is longer) prior to first study treatment administration.

27. Current or recent use (within 1 month or 5 half-lives whichever is longer) of glucagon-like peptide-1 (GLP1) receptor agonists.

28. Any biological compound for research or medical reasons within 12 months prior to (first) study treatment administration.

29. Any relevant bacterial, viral, fungal, or protozoal infection that manifested within the last 6 weeks prior to screening and/or an ongoing relevant bacterial, viral, fungal, or protozoal infection, as judged by the investigator, and/or evidence of immune dysfunction based on laboratory tests at screening. If mild infections occur during screening causing a rise in C-reactive protein (CRP), that is ≥10.0 mg/L, the participant should not be included until this has normalized.

30. Receipt of vaccine within 5 weeks prior to admission.

31. Any medical history of an active tuberculosis (TB) infection, positive test result for latent TB in the last 2 years, or any contact with TB-positive individuals in the last 4 weeks prior to screening.

32. Potential anticipated lack of compliance with study assessments and visit schedule.

33. Planned hospitalization (other than for study assessments) or surgery during the study.

34. Part A Food effect cohort only: Inability or unwillingness to completely consume the high-fat breakfast prior to study treatment administration.

35. Parts B and C only: Pregnant or lactating women.

36. Part B (for those undergoing LP): Contraindications for LP including, but not limited to space-occupying lesions with mass effect or raised intracranial pressure, posterior fossa mass, anticoagulant or antiplatelet medications, coagulopathy, thrombocytopenia (\<150×109/L), congenital spine abnormality, skin infection at the LP site or tattoo covering puncture site.

37. Part B (for those undergoing LP): Lower back pain at the time of the study or history of recurrent headaches in the last 6 months (more than 4 days a month of headaches that limit normal daily activity)

What this study is about