Note: Enrollment in cohort 3 is ongoing
The phase 1 trial of JK07 is a randomized, double-blind, placebo-controlled, dose-escalation study. The interim analysis of this phase Ib data includes eleven NYHA II/III subjects across three single-ascending dose cohorts. Following completion of enrollment in the first two cohorts, administration of JK07 led to dose-dependent improvements in LVEF, with an average improvement of 30% observed at day (D) 90 in Cohort 2 (0.09mg/kg). The unblinded sentinel subject in Cohort 3 (0.27mg/kg) has shown a 70% improvement from baseline at D30 (the absolute improvement from 22% to 38%).
Note: n=4 and n=1 reference table 1 the study cohort
In contrast, placebo subjects (n=2) showed a 4% average improvement in EF at D30 and a decline of 14% on D90.
Moreover, dose-dependent increases in biomarker surrogates of target engagement were observed in each JK07-treated subject across the three cohorts, indicating that target engagement has not yet been saturated. JK07 has been generally well-tolerated in the study, with no serious adverse events (SAEs) reported to date.
The data showed that JK07 Cohort 2 EF improvement is comparable to similar drug at the same dose (dose converted), except that no dose-limiting toxicity was observed with JK07. JK07 Cohort 3, therefore, represents the potential for new levels of activity not seen before in neuregulin clinical studies.
①Lenihan et al. A Phase I, Single Ascending Dose Study of Cimaglermin Alfa (Neuregulin 1β3) in Patients With Systolic Dysfunction and Heart Failure. JACC Basic Transl Sci. 2016 Dec 26;1(7):576-586.