1785-P: Safety, Tolerability, PK, PD, and Exploratory Efficacy of BC-006, an INHBE siRNA: FIH Randomized, Double-Blind, Placebo-Controlled, Single Dose-Escalation Study

Introduction and Objective: BC-006 is a novel GalNAc-conjugated siRNA designed to silence the expression of INHBE, a hepatokine that regulates adipose energy metabolism. It is in development to achieve long-term benefits in body composition, to restore metabolic health, and to improve tolerability when used in treating obesity with or without GLP-1. We report the results of a single dose of BC-006 in healthy subjects with elevated BMI. Methods: Thirty-two participants were randomized (3:1) to receive 1 of 4 ascending BC-006 SQ doses and followed for 85 days to evaluate safety, tolerability, PK, PD, and efficacy. In addition to labs and safety reporting, obesity and lipolysis biomarkers and body composition with DXA were evaluated. After initial study period, subjects returned for an additional 85 days of open-label PD measurements. Results: BC-006 was generally safe and well tolerated, with only mild ISRs reported vs. placebo. PK was predictable and informative for dose selection. INHBE levels revealed potent and durable dose-dependent target knockdown in all clinically relevant doses, with persistent suppression in many subjects past the 6-month open label follow up. Exploratory PD biomarkers showed dose-dependent changes in most BC-006 subjects, with more prominent trends in Adiponectin and FFAs. DXA scans revealed trends in reductions for overall body fat with maintenance of lean muscle mass. Mean visceral fat reductions were 6-8% for BC-006 subjects vs. 5% increase for placebo. Conclusion: In this FIH phase 1b study, BC-006 results in subjects with elevated BMI were consistent with pre-clinical NHP findings. Improvements in both obesity biomarkers and DXA results are encouraging for BC-006 moving into phase 2. In phase 2a, BC-006 will be evaluated after a GLP-1 run-in, and also when administered in combination with GLP-1, with the aim of promoting physiologic and healthy long-term weight maintenance. Disclosure T.M. Hobbs: Employee; Current; BaseCure Therapeutics. Employee; Ended; Diasome. C. Canizares: None. P. Pandarinathan: None. J. Yang: None. J. Kerr: None.