First-time-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RB201 in Healthy Adult Subjects

Treatment: RB201 - small molecule inhibitor of MALT1 Dosage Formulation: Capsule Route: Oral Experimental: Part 1: Single ascending dose (SAD) in up to six dose cohorts (10 mg, 25 mg, 75, 150, 250, and 375 mg by mouth once daily), including one cohort to evaluate the effect of high-fat food on the PK profile (the 150 mg cohort). Total of eight subjects per dose cohort (including the food effect cohort): the first two subjects will be sentinel subjects, randomized 1:1 to receive RB201 or placebo. The next six subjects will be randomized 5:1 to receive RB201 or placebo. Subjects will be housed at the Phase 1 unit and dosing administered and verified (to ensure adherence) by the staff. Part 1 (food effect): The food effect cohort will have one dose administered in a fasted state as in all the other SAD cohorts. Then after a suitable washout period as determined by half-life PK data from prior cohorts, another dose will be administered but this time following a high-fat high-calorie breakfast to eat prior to the second dose. This meal will contain standard high-fat breakfast foods such as eggs, bacon, toast with butter, hash browns and a cup of full cream milk. The participants are instructed to "finish as much of the meal as you can within 30 minutes prior to dosing." They will then undergo safety assessments and PK testing. Part 2: Multiple ascending doses (MAD) for 7 days in two dose cohorts (provisionally 75 mg and 150 mg). These doses will be determined by the sponsor after discussion with the SMC based on safety and PK data from the SAD cohorts. Within each cohort, eight subjects are randomized two to receive placebo and six to receive RB201. The MAD cohorts will be initiated once the equivalent SAD cohort has been completed through Day 7 and the SMC has approved dose-escalation to the next or later SAD cohort(s), such that the anticipated steady state PK exposure in the MAD cohort is estimated to be less than or equal to the PK exposures that demonstrated safety in the SAD portion of the study. Subjects will be housed at the Phase 1 unit and dosing administered and verified (to ensure adherence) by the staff.