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

Cardio R&D

Heart Failure Epidemiology

Heart failure (HF) consists of two primary forms of the disease:

  • 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.

JK07 Design and Rationale: Selective HER4/ErbB4 Agonist

JK07 Diagram

NRG/ErbB4 Pathway: Unique Regenerative Potential in Cardio

NRG-1 is a growth factor that has shown great promise as a treatment for heart failure. It acts through two different pathways – ErbB2/ErbB4 and ErbB2/ErbB3. ErbB4 activation plays a critical role in myocardial development, homeostasis and repair1. In animal studies NRG-1 has shown marked amelioration of several HF features1. Several trials have also reported that administration of NRG-1 can improve hemodynamics and left ventricular function.

However, NRG-1 has a short half-life in circulation2, requiring higher doses to be administered, which has shown signs of toxicity. Dosing has also been limited by gastrointestinal side-effects and a theoretical risk of stimulating cancer progression, primarily by activating the ErbB2/ErbB3 pathway.

NRG/ErbB4 Pathway: Unique Regenerative Potential in Cardio

1. Pentassuglia L, Sawyer DB. The role of Neuregulin-1beta/ErbB signaling in the heart. Exp Cell Res. 2009 Feb 15;315(4):627-37.

2. Lenihan DJ, et al. A Phase I, Single Ascending Dose Study of Cimaglermin Alfa (Neuregulin 1β3) in Patients With Systolic Dysfunction and Heart Failure. JACC Basic Transl Sci. 2016 Dec 26;1(7):576-586.

Positive 6-Month Data from the Phase 1b Clinical Trial of JK07 in Patients with HFrEF

In the completed Phase 1b trial, fourteen patients were dosed with single escalating doses of JK07 and monitored over 180 days for safety and exploratory efficacy. Meaningful improvements were observed across all dose groups compared to placebo, with a ≥31% average improvement in ejection fraction (EF) at the mid and high dose levels. Robust dose-dependent changes were also seen in a biomarker of target engagement.

JK07 was well-tolerated with most adverse events mild to moderate. Only one serious adverse event occurred (Grade 3), at the top dose level.

Dose-dependent target engagement

NT pro-BNP increased transiently, indirectly demonstrating target engagement1

Longer term data shows return to baseline

NT pro-BNP percent change from baseline, Day 2

1. Cassady E. Rupert and Kareen L. K. Coulombe. IGF1 and NRG1 Enhance Proliferation, Metabolic
Maturity, and the Force-Frequency Response in hESC-Derived Engineered Cardiac Tissues. Stem Cells International
Volume 2017, Article ID 7648409, 13 pages

NT pro-BNP absolute change from baseline, Day 1 - 180

* 0.09 mg/kg: n=3 at D135/180
** 0.27 mg/kg: n=2 at D135/180

Change in left ventricular ejection fraction (LVEF) after single-dose of JK07

Absolute change from baseline

Based on these positive initial findings, SalubrisBio has initiated a Phase 2 clinical trial to further evaluate JK07 in HFrEF and HFpEF, and is actively recruiting patients.