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Data from a phase 1b trial presented at HFSA 2023 detail the effects of JK07, an investigational agent from Salubris Biotherapeutics, in patients with heart failure with reduced ejection fraction.
Data from a phase 1b trial of JK07 suggests the agent could prove beneficial in the management of heart failure with reduced ejection fraction (HFrEF).
A recombinant fusion protein from Salubris Biotherapeutics, results of the study suggest use of the agent was associated with a 31% improvement in mean ejection fraction with the mid- and high-doses of the agent, with the company disclosing plans to initiate a phase 2 repeat-dose study in patients with heart failure with preserved ejection fraction in the first half of 2024.1,2
“We are highly encouraged by the meaningful improvements in ejection fraction JK07 has demonstrated through 6 months following a single dose,” said Sam Murphy, chief executive officer of SalubrisBio.2
An ErbB3 antagonist antibody fused with the active domain of a fully human recombinant Neuregulin-1, JK07 is designed to activate multiple ErbB4-mediated cell signaling cascades to facilitate reverse modeling and angiogenesis. Presented at the Heart Failure Society of America (HFSA) 2023 Annual Scientific Meeting, the current phase 1 single-ascending dose trial was launched with the intent of assessing the safety, pharmacokinetics, and exploratory activity of JK07 in subjects with HFrEF.1
For inclusion in the trial, patients were required to have HFrEF, NYHA class II-III symptoms, aged 18-80 years, and be on stable guideline-directed medical therapy. A total of 14 subjects were enrolled in the trial.1
From this group, 5 were place in each of the first 2 dose cohorts and the remaining 4 were randomized to the third dose cohort. Investigators pointed out the first subject in each cohort were considered active sentinel and the following subjects were randomized in a 3:1 ratio to JK07 or placebo therapy. Investigators also pointed out the doses in the first two cohorts were 0.03 and 0.09 mg/kg, respectively, while the third dose cohort was 0.27 mg/kg.1
In the HFSA 2023 presentation, investigators relayed data suggesting there were no dose-limiting toxicities, hepatoxicity, cardiac rhythm abnormalities, or injection site reactions observed during the 180-day follow-up period. Further analysis suggests grade 1 adverse events were observed in 1 of 4 subjects at 0.03 mg/kg, grade 1-2 adverse events were observed 3 of 4 subjects at 0.09 mg/kg, grade 1-3 adverse events were observed in 3/3 subjects at 0.27 mg/kg, and grade 1 adverse events were observed in 1 of 3 placebo subjects.1
Additionally, investigators highlighted a dose-dependent left ventricular ejection fraction improvement within the first 15 days post-dose through the end of the study. Specifically, the mean absolute increase in LVEF at Day 180 was 2% in the 0.03 mg/kg group, 12% in the 0.09 mg/kg group, 7% in the 0.27 mg/kg group, and 2% in the placebo group. Analysis of change in NT-proBNP revealed transient, dose-dependent increases, which returned to baseline by day 30 across all three doses.1
“The durable and sustained responses observed to date suggest that JK07 has the potential to improve functional capacity, quality of life, and long-term outcomes for these patients, who currently have limited treatment options. We are pleased to be advancing JK07 into a multiple-dose Phase 2 study in both HFrEF and HFpEF to further evaluate its clinical potential in these prevalent heart failure populations,” Murphy continued.2