Rapid Detection of Sepsis

The ability to diagnosis sepsis rapidly and accurately in its early stages remains one of the biggest challenges faced by hospitals. Early detection is critical to improved outcomes for patients and more efficient use of health care resources.

DSX has discovered and proven that a specific protein is only found in blood of people suffering from the onset of sepsis. This protein, an enzyme called inducible nitric oxide synthase (iNOS) is centrally involved in the pathology of sepsis and functions as an initiator of organ dysfunction, damage, and death. DSX has completed three proof-of-concept clinical trials with 350 patients and more than 1200 blood samples and has successfully demonstrated our biochemical diagnostic test can detect sepsis early, even before other physiological symptoms appear.

Sepsis has very low Standard Of Care in hospitals

There is currently no effective therapeutic treatment for sepsis. DSX Therapeutics is striving to change this deplorable situation. It has developed the first effective therapeutic product, aSeptiMab™, to treat sepsis and severe sepsis. DSX has also developed the first accurate IVD test to diagnose sepsis pathology early.

The detection of iNOS in plasma can be used to initiate current “standard of care” therapies, such as broad spectrum antibiotics and antifungals. Everyone in the sepsis field agrees that the earlier effective treatment can be applied the better the outcome for the patient. Our IVD test detects the onset of the pathology 24 – 48 hours earlier than the attending physicians can see the physiological symptoms of the sepsis pathology.

Data from our 3rd clinical trial was analyzed to determine if iNOS could predict organ damage in trauma patients associated with the sepsis pathology (Table below). These analyses showed our IVD test for iNOS predicted hemodynamic, pulmonary and renal dysfunction associated with sepsis for trauma patients, and had a positive predictive value of 96% and negative predictive value of 80%. The sensitivity of the IVD test was calculated to be 88% and the specificity was calculated to be 92%. The PPV, NPV, sensitivity and specificity assay characteristics are remarkable since our trial was not designed to generate data to answer this type of regulatory agency question. Our trials were designed to generate data to answer very basic scientific questions, such as is iNOS present in the plasma of septic patients. Unfortunately, not all the patients in our clinical studies had blood cultures done and the MDs didn’t always note on the patient’s chart if they suspected sepsis. Thus, for some of the patients in our clinical studies it was impossible to correlate plasma iNOS with the sepsis pathology. Therefore, we analyzed our clinical data for trauma patients based upon the functioning of the three organs MDs follow the closest for the onset of sepsis, namely the heart, lungs and kidneys.

Plasma iNOS Predicts Hemodynamic, Pulmonary and Renal
Dysfunction in Trauma Patients

PPV = positive predictive value and NPV = negative predictive value. These analyses were based upon the follow criteria: [1] hemodynamic dysfunction was defined as mean arterial pressure (MAP) < 70 mm Hg or the patient was receiving one or more pressor drugs; or [2] renal dysfunction was defined as blood urea nitrogen (BUN) > 20 mg/dl; or [3] pulmonary dysfunction was defined as a diagnosis of respiratory failure or mechanical ventilation for > 24 hours or SIMV with changes in blood gasses and pH.

Therapeutic

DSX Therapeutics' aSeptiMab™ is a chimeric monoclonal antibody (MAb) that has been genetically engineered to specifically target and neutralize microvesicle-associated iNOS (MV-A iNOS). Data from pre-clinical studies show an intravenous infusion of aSeptiMab™ can neutralize in vivo the deleterious effects of MV-A iNOS. DSX Therapeutics' aSeptiMab™ is the first truly effective treatment for sepsis and severe sepsis.

1. aSeptiMab™ enters blood stream via IV
2. Mab binds to epitope on circulating MV-A iNOS protein antigen
3. neutralized Ag-Ab complex is cleared from the blood
4. liver metabolizes and destroys MV-A iNOS