Heart Failure Epidemiology

Heart failure (HF) classification consists of two primary forms of the disease: Heart Failure with Reduced Ejection Fraction (HFrEF) and Heart Failure with Preserved Ejection Fraction (HFpEF), which each represent approximately 50% of the overall HF patient population.

There are treatments available for patients with HFrEF, but clinical progression and death still occur.  For HFpEF, there is not a single approved drug or device to date – half of all HF patients have no treatment option available to them.

Neuregulin-1

Neuregulin-1, also known as NRG-1 or simply neuregulin, is a growth factor that has shown great promise as a treatment for heart failure.

In animal studies, neuregulin 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

Improvement in left ventricular ejection fraction following NRG-1 administration

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.

Researchers have shown the NRG-1 acts through two different pathways – HER3 and HER4.  The HER3 pathway appears primarily responsible for the GI side-effects and the cancer risk, while the HER4 pathway appears primarily responsible for the regenerative effects in the heart.

There is a belief in the research community that selectively activating HER4 without activating HER3 could yield a wider therapeutic window and better clinical effects.

JK07 Design

JK07 Diagram
  • NRG-1 fusion domain can stimulate HER3 and HER4
  • Anti-HER3 antibody blocks HER3 signaling
  • Overall effect is selective stimulation of HER4 with a favorable pharmacokinetic profile
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.