- Heart Failure with Reduced Ejection Fraction (HFrEF) happens when the heart muscles fail to contract properly to pump an adequate amount of oxygen-rich blood to other parts of the body.
- Heart Failure with Preserved Ejection Fraction (HFpEF), occurs when the lower left chamber of the heart (left ventricle) is not able to fill properly with blood, resulting in less blood being pumped though out the body.
While there are several treatments available for HFrEF, disease progression and death still occur. There are only two approved treatment options currently available for patients living with HFpEF.
Neuregulin-1 (NRG-1)
NRG-1, is a growth factor that has shown great promise as a treatment for heart failure.
In animal studies, NRG-1 has been shown to improve heart function in a variety of different models of heart failure.
In clinical studies, the growth factor by itself showed the ability to improve ejection fraction in HFrEF patients by nearly 10% absolute improvement at higher doses – a statistically significant and clinically meaningful improvement.
Improvement in left ventricular ejection fraction following NRG-1 administration
Phase 1b clinical study with recombinant NRG-1 in patients with HFrEF
Click image to enlarge
Vermeulen et al., ErbB2 signaling at the crossing between heart failure and cancer,
Basic Res Cardiol (2016) 111:60
However, NRG-1 by itself has a short half-life in circulation. This requires higher doses to be administered, which have shown signs of toxicity, or for administration over a prolonged period of time – 10 hours per day for 10 consecutive days in Phase III studies.
NRG-1 dosing has also been limited by gastrointestinal (GI) side-effects and a theoretical risk of stimulating cancer progression.
NRG-1 acts through two different pathways – HER3 and HER4. The HER3 pathway appears primarily responsible for GI side-effects and cancer risk, while the HER4 pathway appears primarily responsible for regenerative effects in the heart.
Selectively activating HER4 without activating HER3 could yield a wider therapeutic window and better clinical effects.
SalubrisBio is developing JK07, a recombinant fusion protein consisting of a fully human immunoglobulin IgG1 monoclonal antibody and an NRG-1, that has the potential to significantly widen the therapeutic window of NRG-1 and yield better clinical effects. JK07 is being clinically evaluated in ongoing Phase 1b clinical trial in patients with HFrEF and HFpEF. The Phase 2 portion of the HFrEF study is expected to begin in the second half of 2023.
JK07 Design and Rationale: Selective HER4/ErbB4 Agonist
JK07 has shown potent regenerative potential in large and small animal models of heart failure, including HFrEF and HFpEF, and potent anti-tumor activity in a xenograft model of cancer.
Enrollment in the Phase 1b portion of the study is complete; data from this study will be presented at a forthcoming medical meeting.
Learn more about our cardiology clinical trials:
Heart Failure Facts
Heart failure is the leading cause of death in the U.S., with close to 400,000 deaths attributable to heart failure annually1
An estimated 6.5 million people are living with heart failure in the U.S. today and 960,000 new cases are diagnosed each year2
From the time of diagnosis, more than half of heart failure patients die within five years – a worse prognosis than some cancers3
In addition to the burden on patients and hospitals, the economic cost of heart failure in the U.S. is estimated to be >$30 billion dollars4