At the 2021 American College of Allergy, Asthma and Immunology Annual Scientific Meeting, Astria Therapeutics, Inc. presents new preclinical data including demonstration of the high potency of STAR-0215 to bind to and inhibit plasma kallikrein on a site different than lanadelumab and introduction of YTE technology to extend half-life.
“These preclinical data support the potential of STAR-0215 to provide long-acting, effective prevention of HAE attacks, with dosing once every three months or longer,” says Andy Nichols, Ph.D., Chief Scientific Officer at Astria. “These data show that STAR-0215 binds to plasma kallikrein with high affinity and inhibits its activity more potently than lanadelumab, a plasma kallikrein inhibitor on the market for the treatment of HAE. Combined with the long plasma half-life from the YTE modifications and high potency, we believe that STAR-0215 has a differentiated profile that has the potential to be the most patient-friendly preventative treatment option for HAE.”
Plasma kallikrein binding affinity and plasma half-life are key drivers of efficacy for the prevention of HAE attacks. The data show that STAR-0215 binds to plasma kallikrein in vitro with high affinity, about ten-fold more potently than lanadelumab, a monoclonal antibody plasma kallikrein inhibitor. In addition, in competition binding experiments, STAR-0215 was shown to bind to a different site on plasma kallikrein than lanadelumab. YTE modifications in STAR-0215 are designed to enable a longer duration of action. In cynomolgus monkeys dosed with STAR-0215, the enhanced FcRn binding enabled by the YTE modifications translated to a more than three-fold increase in plasma half-life to about 34 days with STAR-0215 compared to an antibody without the YTE modifications. The plasma half-life of STAR-0215 in cynomolgus monkeys was also more than three-fold longer than that of lanadelumab, supporting the potential for less frequent dosing.
STAR-0215’s potency was also tested using a physiologically relevant assay. STAR-0215 potently inhibited the release of bradykinin from high molecular weight kininogen, with an IC90 about 10-fold more potent than the IC90 achieved by lanadelumab in the same assay. IC90 corresponds to the concentration required to inhibit 90% of enzymatic activity, which is thought to be the level of plasma kallikrein inhibition required to prevent HAE attacks. Pharmacokinetic/pharmacodynamic modeling showed that STAR-0215 is predicted to prevent HAE attacks for a substantially longer period than lanadelumab. Based on these data, STAR-0215 has the potential to be administered once every three months or longer to effectively prevent HAE attacks.
Astria’s goal is to provide the most patient-friendly preventative treatment option for people living with HAE. The company expects to file an Investigational New Drug application for STAR-0215 in mid-2022 and plans to initiate a Phase 1 clinical trial with initial results anticipated by year end 2022.
(Source: Astria)
