ExThera’s proprietary Seraph® Microbind® Affinity Blood Filter is a first-of-its kind technology designed to capture and remove a broad range of bacteria, viruses, toxins and pro-inflammatory cytokines from whole blood. Validated in preclinical studies and currently under evaluation in a first-in-man clinical trial in Europe, the device promises to address significant unmet needs for immediate treatment in instances of either known or unknown bloodstream infections.
Seraph’s very broad spectrum ability to remove pathogens without harming the treated blood gives it many potential applications. The company is currently evaluating the therapeutic use of Seraph in a dialysis-like extracorporeal circuit for treating patients with both drug-resistant and drug-susceptible bloodstream infections. Another important potential use is in blood banking, as a simple and safe pathogen reduction technology for treating individual units of blood, to reduce the threat of disease transmission via transfusion.
How It Works
As a patient's blood flows through the Seraph® Microbind® Affinity Blood Filter, it passes over proprietary microspheres coated with molecular receptor sites that mimic the receptors on human cells that pathogens use when they invade the body. Harmful substances are captured and adsorbed onto the device’s proprietary surface and thereby removed from the bloodstream without adding anything to the treated blood, which is returned to the patient’s body with blood cells intact. The adsorption media is a flexible platform that uses chemically-bonded, immobilized heparin for its unique binding capacity, and may be configured with optional supplemental adsorbents to accommodate evolved pathogens. The blood filter uses an inexpensive, naturally occurring blood-contacting surface that is anti-thrombogenic and anti-inflammatory, and which has been proven to be safe in other medical devices and implants.
Seraph has been engineered to operate with a low-pressure drop at blood flow rates up to 350 mL/minute, offering efficiency in treatment, and economical use with existing equipment. Unlike other technologies which attempt to capture molecules based on their size or antibody affinity, Seraph uses the biological activity of naturally-occurring ‘ligands’ to remove both molecules and cellular pathogens by selective adsorption.
In preclinical studies, ExThera’s scientists have demonstrated that many toxins, inflammatory cytokines and a wide variety of pathogens are captured by Seraph when whole blood or serum is passed through the device. Notably, in vitro studies have demonstrated that both S. aureus and MRSA are bound to the Seraph hemofilter's adsorption media as blood passes over it, allowing the concentration of bacteria in the bloodstream to be reduced by up to 85 percent in just a single pass of contaminated blood. Reducing the patient's pathogen load in blood should lower the body's risk of metastatic infection and a dysfunctional host response stemming from the release of a variety of virulence factors, toxins, and cytokines.
ExThera has also developed supplemental adsorption media which capture the pathogens and toxins that do not naturally bind to heparan sulfate. Included in this group are endotoxin, Pseudomonas aeruginosa, and B. anthracis.
Seraph is supported by a robust, comprehensive research and development program, including multiple, company-sponsored pre-clinical studies, conducted at independent university and commercial laboratories. As well as having served as the foundation of the company’s clinical trial program, this work has produced a growing body of peer reviewed published literature.
Defense Advanced Research Programs Agency (DARPA) - DLT
Seraph is being evaluated in partnership with Battelle Memorial Institute to develop a “Dialysis-Like Therapeutics” (DLT) device to treat sepsis in wounded warriors, under a grant from DARPA.
Dialysis Patient Infections
Dialysis patients must rely on infection-prone vascular access sites, that contribute to bloodstream infections. This poses a constant threat to their overall health and wellbeing, especially within the first six months after beginning treatment. (1,2) Significantly, bloodstream infections are the second leading cause of death in this patient population. (3) Because nephrologists are on the frontlines in the battle against bloodstream infections, they are ideal partners for ExThera’s clinical trials of Seraph in dialysis patients infected with Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA).
ExThera Medical has therefore selected the hemodialysis patient population as its first group for clinical investigation. The company has begun its first clinical trial in Europe, and is enrolling patients at its clinical trial sites.The company is also in discussions with the FDA for approval of its U.S. Investigational Device Exemption, which is expected to lead to the start of U.S. clinical trials in the near future.
1) Engemann, John J., et al. "Clinical outcomes and costs due to Staphylococcus aureus bacteremia among patients receiving long-term hemodialysis." Infection Control & Hospital Epidemiology 26.06 (2005): 534-539.
2) Powe, Neil R., et al. "Septicemia in dialysis patients: incidence, risk factors, and prognosis." Kidney international 55.3 (1999): 1081-1090.
3) Wang, I-Kuan, et al. "Bacteremia in hemodialysis and peritoneal dialysis patients." Internal Medicine 51.9 (2012): 1015-1021.