Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, today announced positive updated results from the completed Phase 1b study of JK07 in patients with HFrEF. The data were presented in a late breaking oral session during the Heart Failure Society of America Annual Scientific Meeting 2023. JK07 is the first investigational antibody fusion protein and first selective ErbB4 agonist to enter clinical development for heart failure. Heart failure is a leading cause of morbidity and mortality globally, with estimates of more than 6 million patients affected by HFrEF and HFpEF in the US.
“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. “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 repeat-dose Phase 2 study in both HFrEF and HFpEF to further evaluate its clinical potential in these prevalent heart failure populations.”
In the completed Phase 1b study, fourteen patients were randomized 3 to 1 active treatment to placebo (11 JK07 : 3 placebo), with five patients in each of the first two cohorts (0.03mg/kg and 0.09 mg/kg, respectively), and four in the third cohort (0.27 mg/kg). Single doses were administered intravenously and changes from baseline values of left ventricular EF were measured for each patient.
Key findings include:
- Robust dose-dependent changes in a biomarker of target engagement
- Meaningful changes in LVEF observed across all dose groups in comparison with placebo:
| Placebo | 0.03 mg/kg | 0.09 mg/kg | 0.27 mg/kg | |
| Mean Baseline LVEF (absolute) | 31% | 34% | 28% | 25% |
| Relative mean change from baseline at Day 30 | +4% | +20% | +19% | +22% |
| Relative mean change from baseline at Day 60 | -6% | +14% | +28% | +50% |
| Relative mean change from baseline at Day 90 | -19% | +9% | +27% | +14% |
| Relative mean change from baseline at Day 135 | -33% | +5% | +23% | +43% |
| Relative mean change from baseline at Day 180 | +10% | +7% | +49% | +31% |
- JK07 has been generally well-tolerated with most adverse events mild to moderate. Only one serious adverse event occurred (Grade 3), at the top dose level.
A double-blind, randomized, multiple-dose Phase 2 trial of JK07 in patients with HFrEF and HFpEF is expected to begin in 1H 2024.
About Heart Failure
Heart failure affects an estimated 6.2 million Americans[i] and more than 64 million people worldwide[ii]. Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) each affect over 3 million patients in the US alone. Heart failure is a chronic condition in which patients experience progressively worsening symptoms and quality of life, hospitalizations and death. In HFrEF, the left ventricle loses its ability to contract normally, and the heart cannot pump with sufficient force to push enough blood into circulation. In HFpEF the heart becomes stiff and loses its ability to function properly. JK07 is in development for the treatment of both HFrEF and HFpEF.
About JK07
JK07 is a recombinant fusion protein consisting of a fully human immunoglobulin IgG1 monoclonal antibody and an active polypeptide fragment of the human growth factor neuregulin [NRG-1]. NRG-1 is a clinically validated growth factor that has shown promising activity in heart failure, but also undesirable side effects. Research has shown that NRG-1 induces signaling through interaction with two different receptors – ErbB3 and ErbB4. The ErbB4 pathway appears to be responsible for the regenerative effects in the heart, while the ErbB3 pathway appears primarily responsible for safety and tolerability limitations of recombinant NRG-1. By blocking ErbB3 signaling with an antibody fusion design, JK07 selectively stimulates the ErbB4 pathway with a favorable pharmacokinetic profile, which has the potential to significantly widen the therapeutic window of NRG-1 and yield better clinical effects.
[i] Centers for Disease Control and Prevention, Heart Failure, https://www.cdc.gov/heartdisease/heart_failure.htm, (accessed May 8, 2023).
[ii] Groenewegen, A., Rutter, F., Mosterd, A., & Hoes, A. (2020). Epidemiology of heart failure. European Journal of Heart Failure, 22(8), 1342-1356. https://onlinelibrary.wiley.com/doi/10.1002/ejhf.1858