DecImmune is developing peptide and antibody therapeutics to treat acute inflammation and prevent tissue damage following vascular injury by inhibiting the cascade initiated by the N2-IgM association. The company's lead program, currently in advanced preclinical development, is aimed at treating myocardial infarction. The company has earlier stage programs to develop therapeutics for treating second degree burns and accelerate graft function and prevent reperfusion injury in transplant patients. The therapeutic candidates also have potential use in stroke, wound trauma and plastic surgery. DecImmune's candidates are protected by two issued patents and multiple pending patent applications.
Myocardial Infarction
Myocardial infarction affects 1.2 million people in the U.S. annually, and causes 450,000 deaths, according to the American Heart Association. Acute inflammation resulting from reperfusion of hypoxic vascular endothelial cells is a significant contributor to cardiac tissue damage. An estimated 25 percent of cardiac damage in myocardial infarction is due to reperfusion injury. While existing therapies such as beta blockers and ACE inhibitors aim to reduce stress on surviving tissue they do not prevent or minimize acute tissue damage.
In initial preclinical studies, published in Cardiovascular Research, researchers at DecImmune and in the laboratories of the company's founders demonstrated that both a synthetic N2 peptide and anti-N2 antibodies are protective in a murine model of cardiac reperfusion injury. Administration of the N2 peptide 90 minutes after ischemia reduced infarct size by 33 percent and troponin-I release by 41 percent, providing a realistic time window for treatment in a critical care setting. The company is conducting additional preclinical studies in support of an IND to begin clinical trials. The research is also being supported through a Phase 2 SBIR grant.
N2 Peptide Protects Against Cardiac Injury in Myocardial Infarction Model
In a mouse model of myocardial infarction, mice were administered N2 peptide prior to restoring blood flow to the blocked vessel in the heart. Infarct size and troponin-I, a serum marker for cardiac injury, were measured at 24 hours. Mice treated with N2 peptide had significantly reduced infarct sizes and serum troponin-I levels indicating N2 peptide provides protection from cardiac injury as a result of myocardial infarction. Based on data published in Cardiovascular Research (online), June 2010.
Burn Injury
An estimated 50,000 people are treated for burns in the U.S. annually and 40,000 patients require hospitalization, according to the American Burn Association. There are an estimated 4,000 deaths due to burn related complications. Acute inflammation is implicated in amplifying the depth of burn injury, which can result in increased scarring and a need for surgical skin grafting. In murine studies published by in the Proceedings of the National Academy of Sciences, DecImmune's founders demonstrated that activation of N2 pathway is central to exacerbating scald burn wound depth and that burn injury is limited by administration of an N2 peptide. The research is supported by a $1.8 million Phase II SBIR grant from the National Institutes of Health.
Transplantation
Ischemia/Reperfusion injury results in delayed graft function (DGF) in up to 40% of liver and kidney transplants, particularly in cadaveric transplants. DGF results in the transplanted organ underperforming and for renal transplants this often means the need for continued dialysis support for the patient. There are approximately 40,000 kidney transplants each year in the US, Europe and Japan. Of the 16,500 kidney transplants in the US each year, 65% are cadaveric.
There is currently no approved therapeutic to address renal transplant reperfusion damage. Prophylactic treatment with and N2 targeting therapeutic during organ reperfusion has the potential to significantly suppress the acute inflammatory response that leads to DGF. DecImmune is currently conducting preliminary investigation to characterize potential for this indication.