Cardio R&D
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.
NRG/ErbB4 Pathway: Unique Therapeutic 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.
JK07 Design and Rationale: Selective ErbB4 Agonist
Phase 1b Study of JK07 in HFrEF Subjects Showed Durable Improvement in Left Ventricular Ejection Fraction (LVEF) Following a Single Dose
Ongoing Phase 2 Study Evaluating JK07 in HFrEF and HFpEF: Positive Interim Data
Results from the first 68 randomized subjects demonstrated:
- A safe and tolerable profile at the 0.045 mg/kg dose
- Clear and consistent target engagement with repeat administration
- Positive preliminary signs of efficacy
- No meaningful differences in adverse event (AE) frequency and severity between active and placebo groups
The study is expected to enroll 282 subjects randomized (2:1) to receive multiple doses of JK07 or placebo.
Based on these positive initial findings, SalubrisBio has opened up the 0.09 mg/kg dose treatment arm of their Phase 2 clinical trial to further evaluate JK07 in HFrEF and HFpEF and is actively recruiting patients.
Heart Failure Facts
Heart Failure is the leading cause of death in the U.S., with close to 450,000 deaths attributable to Heart Failure annually1
An estimated 6.7 million people are living with Heart Failure in the U.S. today and 960,000 new cases are diagnosed each year1, 2
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