AB-729 (GalNAc-RNAi)

AB-729 is a subcutaneously-delivered RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral antigens, including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus.  AB-729 targets hepatocytes using our novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology. 
 

AB-729 is currently being evaluated in a Phase 2a randomized, open-label, proof-of-concept clinical trial in combination with ongoing standard-of-care nucleos(t)ide analog therapy and short courses of Peg-IFNα-2a in 40 patients with chronic HBV infection. The primary objective of the clinical trial is to evaluate the safety and tolerability of AB-729 plus Peg-IFNα-2a in subjects with NA-suppressed chronic HBV infection. AB-729 is also being evaluated in several additional phase 2a studies with outside partners in clinical collaborations.

 

Data from an on-going three-part, multi-cohort Phase 1a/1b clinical trial, designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single- and multi-doses of AB-729, has shown that:

 

  • AB-729 is generally safe and well tolerated through 48 weeks of dosing.
  • Repeat dosing of 60mg and 90mg of AB-729 resulted in comparable HBsAg decline profiles with a plateau in response observed around week 20, regardless of dose or dosing interval.
  • Long-term dosing with AB-729 resulted in 75% of patients reaching <100 IU/mL of HBsAg.
  • Preliminary data suggest that long-term suppression of HBsAg with AB-729 results in increased HBV-specific immune response.


We believe that the magnitude and sustained reduction in HBsAg achieved with a 60 mg dose of AB-729 administered every 8 weeks has the potential to provide an important competitive advantage and is an appropriate and convenient dose to explore in future trials.