Lead Indication

SP16 and AMI

The SP16 Challenge – Reduce Morbidity After Acute Myocardial Infarction.

Acute myocardial infarction (AMI, or heart attack) remains a major cause of morbidity and mortality in the world, with roughly 500,000 new cases per year in the U.S. alone. Despite current strategies for early reperfusion (injecting oxygen to the heart), some patients die soon after AMI and those who do survive are at risk of heart failure and not necessarily healthy when they leave the hospital. There is a strong correlation between the severity of AMI and the incidence of other chronic cardiac diseases. Heart failure is now the leading cause of hospitalization for people over 65, with nearly six million patients in the U.S. Despite current therapies, about 30 percent of patients die within five years of a heart attack and onset of heart failure. Clearly, more effective treatments for AMI that reduce massive inflammation are urgently needed if survival rates are to be increased. Unfortunately, no anti-inflammatory drugs currently available can substantially and effectively reduce inflammation within the critical time frame and lower incidents of death.

Serpin’s lead drug candidate SP16, administered after a heart attack, has been shown in multiple models to reduce the danger of inflammation and thus minimize or reduce the severity of catastrophic outcomes. It is the only candidate positioned to fill this gap and has no current competition.

The four FDA-approved products currently on the market for treatment of alpha-1 antitrypsin (AAT) deficiency (Prolastin®, Zemaira®, GlassiaTM, and AralastTM) are purified from human plasma and face manufacturing, supply, and cost challenges. Numerous clinical trials currently under way could expand the use of AAT to treatment of type 1 diabetes, cystic fibrosis, and graft-versus-host disease – applications that could boost the market potential of AAT products to several billion dollars annually and offer major opportunities to Serpin Pharma.

SP16 — Potential Reduction of AMI Outcomes.

After AMI, a close interplay exists between inflammation and adverse cardiac results from scarring and heart failure. Acute myocardial ischemia and infarction initiate an intense inflammatory response within the heart. Leukocytes (white blood cells) infiltrate the damaged myocardium to coordinate tissue repair and infarct healing, leading to newly formed vessels and reparative fibrosis. While limited inflammation is necessary for infarct healing, uncontrolled inflammation causes further damage to the heart and is responsible for nonfunctional healing, which then becomes the basis for adverse cardiac scarring and heart failure.

A single injection of SP16, given in multiple animal models 30 or 60 minutes after administration of oxygen, indicated a reduction of infarct by over 50 percent, a reduction in Troponin (a specific biomarker for cardiac muscle injury) by 90 percent, and close to normal functionality as measured by a traditional echo heart procedure. Several pre-clinical studies conducted at Virginia Commonwealth University by Dr. Abbate’s group (see profile of Dr. Abbate below) show consistently that treatment with SP16 is effective. Studies also show that the cardio-protective effect of SP16 continues for seven days following a single injection. Safety studies performed in mice, rats, and dogs showed that injection of SP16 at very high levels (over 100 times the expected therapeutic human dose) causes no toxicity effects. SP16 therefore represents a new therapeutic class of synthetic anti-inflammatory peptides for preventing inflammatory injury following AMI.