Late Breaking Abstract - Dose-dependent inactivation of airway tryptase with a novel dissociating anti-Tryptase antibody (MTPS9579A) in healthy volunteers

Background: Tryptase is the most abundant secretory granule protein in human lung mast cells and plays an important role in asthma pathogenesis. MTPS9579A is a novel monoclonal antibody that selectively inhibits tryptase activity by dissociating active tetramers into inactive monomers. The safety, tolerability, pharmacokinetics (PK), and airway pharmacodynamics (PD) of MTPS9579A were assessed in healthy volunteers. Methods: The Phase I studies were single-center, randomized, observer-blinded, and placebo-controlled. Single and multiple ascending doses of MTPS9579A were administered subcutaneously (SC) or intravenously (IV) in healthy volunteers. An activity based probe immunoassay was developed and used to specifically measure active tryptase in nasosorption (non-invasive sampling of nasal mucosal lining fluid). Results: This study included 106 healthy volunteers (82 on active). Overall, MTPS9579A was well tolerated with adverse events being predominantly mild or moderate. There were no serious adverse events reported. MTPS9579A showed dose-proportional increase in Cmax values and a half-life of 30-34 days. Rapid and dose dependent reduction in nasosorption active tryptase was observed post-dose, confirming activity of MTPS9579A in the airway. Conclusions: A novel immunoassay was used to demonstrate for the first time that an investigative antibody therapeutic (MTPS9579A) can inhibit tryptase activity in the upper airway. A favorable safety and tolerability profile supports further assessment of MTPS9579A in asthma. PKPD relationship may help inform future trials.