Multiple Ascending Oral Dose 14-Day Trial of LHF-535 in Healthy Participants

Inclusion Criteria:

• Male or female 18 to 50 years of age, inclusive, at the time of screening
• Able to understand the requirements of the study, to provide written informed consent (as evidenced by signature on an informed consent document that is approved by a Human Research Ethics Committee [HREC]), and agreeable to abide by the study restrictions
• Body mass index (BMI) of 18.0 to 35.0 kg/m^2, inclusive, at the time of screening
• Weight between 50 kg and 110 kg, inclusive, at the time of screening and check-in (Day -1)
• Good general health (e.g., no chronic health conditions such as hypertension, diabetes, chronic obstructive pulmonary disease, or cardiovascular disease) as determined by the Investigator; participants with mild allergies or benign conditions such as Gilbert's disease may be enrolled at the discretion of the Investigator
• Female participants of child-bearing potential, with a fertile male sexual partner, must use a highly effective method of contraception (oral contraceptive, intrauterine device, or hormonal patch, injectable, or implantable device) in conjunction with a male condom during the screening period and for the entire duration of study participation including the 28-day follow-up; true abstinence from sexual intercourse with a partner of the opposite sex, in accordance with the preferred and usual lifestyle of the participant, is acceptable; periodic abstinence or avoiding sexual intercourse on days while the participant is fertile (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), are not acceptable methods of contraception; non-childbearing potential is defined as postmenopausal as documented by an elevated follicle stimulating hormone (FSH) level or surgical sterility (e.g., tubal ligation, hysterectomy, and/or bilateral salpingo-oophorectomy)
• Male participants must either be surgically sterile (vasectomy) or agree to use a male condom as a method of contraception for the entire duration of the study and for 90 days after dosing; the female sexual partner must also use a medically acceptable form of birth control (e.g., oral contraceptive)
• Male participants must agree to not donate sperm for the entire duration of the study and for at least 90 days after dosing

Exclusion Criteria:

• Pregnancy or breastfeeding
• A positive screen for drugs of abuse, including alcohol; the screen may be repeated once (on Day-1) at the Investigator's discretion if a false-positive result is suspected
• Use of more than 5 tobacco- or nicotine-containing products per week (including but not limited to: cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 3 months prior to check-in (Day -1) or use of tobacco- or nicotine-containing products within 72 hours of check-in (Day -1) until discharge from the study unit
• Donated blood within 90 days or plasma within 30 days of dosing on Day 1
• Any history of anaphylaxis to medication, food, animal toxin or other substances
• Active substance abuse or any medical or psychiatric condition that could jeopardize the participant's safety
• Use of any medications apart from vitamins, acetaminophen, or hormonal contraception within 14 days of dosing on Day 1 (unless approved by the Investigator and Sponsor Medical Monitor); participants with mild allergies may use antihistamines at the discretion of the Investigator after approval by the Sponsor Medical Monitor
• Receipt of an investigational product within 12 weeks prior to dosing on Day 1 (or 5 half-lives, whichever is longer)
• Any history of cancer; non-melanoma skin cancer or cervical cancer in situ, resected surgically with no evidence of disease, may be enrolled at the discretion of the Investigator
• Receipt of an organ transplant (solid or hematopoietic), including corneal transplant
• Prolonged QTcF interval >450 ms on electrocardiograms (ECGs) collected during screening, on Day -1, or just prior to dosing on Day 1 (following one repeat)
• Other clinically significant ECG abnormality, as determined by the Investigator
• Any clinically significant abnormal hematology, chemistry, or urinalysis value, as determined by the Investigator. Repeat testing is permitted at the discretion of the Investigator
• Positive test for human immunodeficiency virus (HIV serology) or known HIV infection
• Positive result for hepatitis B surface antigen (HBsAg) or for hepatitis C virus (HCV) antibody
• Use of alcohol-containing foods or beverages within 72 hours prior to check-in on Day -1 or 72 hours prior to any study visit
• Use of caffeine-containing foods or beverages within 24 hours prior to check-in on Day -1 until discharge from the study unit
• Strenuous exercise for 24 hours prior to check-in on Day -1 until discharge from the study unit
• Febrile illness or significant infection within 48 hours before administration of the first dose of study drug on Day 1