Phase 1, single center, randomized, double blind, placebo controlled SAD study assessing safety, tolerability, PK, PD, and immunogenicity of HB2198 after a single IV infusion in healthy adults. Four dose levels will be explored with sentinel participants per cohort. Approximately 32 participants (6 HB2198:2 placebo per cohort) will be followed for ~2 months, with extended follow up if B-cell counts remain suppressed.

HB2198 is a tetravalent bispecific antiCD19/CD20 antibody engineered with dual Fc domains (S239D/I332E) to enhance FcγR engagement. Cohorts (n=8 each) receive a single IV dose of HB2198 or placebo under double blind conditions; 2 sentinels (1 active, 1 placebo) are dosed ≥48 h before the remaining 6 participants. Safety/PK/PD and immunogenicity are characterized through Day 28 and to Month 2, including B-cell depletion kinetics, lymphocyte phenotyping, cytokines, quantitative immunoglobulins, and ADAs.

Inclusion Criteria:

• 18-55 years; Healthy Adults
• IgG ≥ 600 mg/dL
• Peripheral B cell count within lab normal range
• Negative pregnancy test (WOCBP) and protocol specified contraception
• Confinement from Day -1 through ≥24 h after Day 1 dosing
• Informed consent

Exclusion Criteria:

• Clinically significant disease that could affect safety or data
• Hypogammaglobulinemia; active/recent significant infection
• Chronic antivirals/antimicrobials
• Recent major surgery; live vaccine <30 days (inactivated ≥14 days before Day 1 recommended)
• Positive TB screen without treatment
• HBV DNA+ or HCV RNA+; HIV+
• Pregnancy/breastfeeding
• Planned conception or gamete donation within 6 months post dose

This is still being actively discussed. A decision will be made during the course of the study.