JK07 Shows Promise for Heart Failure with Reduced Ejection Fraction in Phase 1 Trial

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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

References:

1. Tang WH, Steiner J, Kassi M, et al. Final Analysis Of Safety And Exploratory Echo Data In A Phase 1, First-in-human, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study To Evaluate JK07 In Subjects With Heart Failure With Reduced Ejection Fraction. Paper presented at: Heart Failure Society of America 2023 Annual Scientific Meeting; October 6 - 9; Cleveland, OH. Accessed October 9, 2023.
2. Salubris biotherapeutics presents positive 6-month data from phase 1b clinical trial of JK07 in late-breaking session at the Heart Failure Society of America Annual Meeting 2023. Salubris Biotherapeutics. October 9, 2023. Accessed October 9, 2023. https://www.businesswire.com/news/home/20231009508508/en/Salubris-Biotherapeutics-Presents-Positive-6-Month-Data-from-Phase-1b-Clinical-Trial-of-JK07-in-Late-Breaking-Session-at-The-Heart-Failure-Society-of-America-Annual-Meeting-2023.