B15-09 Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BBT002, a Novel Bispecific IL-4Rα/IL-5 Antibody: Results From the Single- and Multiple-ascending Dose Healthy Volunteers Portions of a Phase I Study

Abstract Background IL-4/13 and IL-5 pathways play a crucial role in chronic obstructive pulmonary disease (COPD) pathogenesis and are associated with a high risk of exacerbations. BBT002 is designed to simultaneously inhibit IL-4/13 and IL-5 pathways with an extended half-life. Targeting these two non-redundant pathways may provide a more efficacious treatment for a broader COPD population. BBT002 showed potent and durable activities in preclinical experiments and was well tolerated in non-human primates. These nonclinical favorable efficacy and safety data supported the initiation of first-in-human (FIH) clinical study of BBT002. Methods BBT002-001 (NCT06944925) is an ongoing randomized, double-blind, placebo-controlled Phase I trial in healthy volunteers (HVs) and adults with COPD or Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and comorbid asthma. The study evaluates safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity following single-ascending dose (SAD) and multiple-ascending dose (MAD) administration. In the SAD phase, HVs were randomized across 5 sequential cohorts to receive a single intravenous infusion of BBT001 at doses ranging from 50 mg to 1200 mg or placebo. In MAD, HVs were randomized to receive repeated intravenous dosing of BBT002 (150-900 mg). Safety assessments included adverse events (AEs), vital signs, laboratory tests, electrocardiograms (ECGs), and physical examinations. Blood samples were collected for PK, immunogenicity (anti-drug antibody, ADA), and PD analyses. Results A total of 41 subjects has been dosed with either BBT002 or placebo in the SAD portion. No dose-limiting toxicities were observed up to 1200 mg, the highest dose tested. No serious or severe (Grade ≥3) TEAEs have been reported. Most TEAEs were mild or moderate in severity and resolved without sequelae. The incidence of treatment-related TEAE was low. No clinically meaningful changes in labs, ECGs, or vital signs were observed. PK analysis demonstrated prolonged half-life at doses greater than 150 mg. The MAD portion of the study is on-going. To-date, safety findings from the MAD portion are consistent with the SAD portion. Comprehensive SAD and MAD data, including safety, tolerability, and PK/PD results, will be presented at ATS. Conclusion BBT002 has been generally well-tolerated as a single dose up to 1200mg. The findings from this study support dose selection and scheduling for subsequent MAD cohorts in patients with COPD or CRSwNP and comorbid asthma, and contribute to the early clinical development profile of BBT002. This abstract is funded by: Bambusa Therapeutics