About Seraph 100
ExThera’s proprietary Seraph® 100 Microbind® Affinity Blood Filter (Seraph 100) is a first-of-its kind, CE Marked, technology designed to reduce bloodborne pathogens during bloodstream infections. Validated in preclinical studies and in a clinical trial in Europe, the device promises to address significant unmet needs for immediate treatment, even before the pathogen is identified.
Seraph’s broad-spectrum ability to reduce the pathogen bioburden without harming the treated blood gives it many potential clinical applications. The company has evaluated the therapeutic use of Seraph 100 in a dialysis-like extracorporeal circuit for treating patients with both drug-resistant and drug-susceptible bloodstream infections.
How It Works
As a patient's blood flows through the Seraph® Microbind® Affinity Blood Filter, it passes over proprietary microbeads coated with molecular receptor sites that mimic the receptors on human cells that pathogens use to colonize when they invade the body. Harmful substances are captured and adsorbed onto the device’s proprietary surface.The adsorption media is a flexible platform that uses covalently-bonded, immobilized heparin for its unique binding capacity. The blood filter mimics a naturally-occurring blood-contacting surface that is anti-thrombogenic and anti-inflammatory, which has been proven to be safe in other medical devices and implants.
Seraph operateswith a low-pressure drop at blood flow rates up to 350 mL/minute, offering compatibility with existing extracorporeal equipment. Some other technologies seek to capture molecules based on their size or physical dimension, but Seraph uses the biological activity of naturally-occurring receptor sites to bind both molecules and cellular pathogens by selective adsorption.
In preclinical studies, ExThera’s scientists have demonstrated that many toxins, inflammatory cytokines and a wide range of bacteria, viruses, toxins and disease-causing sepsis mediators are captured by Seraph when whole blood or serum is passed through the device. Notably, in vitrostudies have demonstrated that MRSA, S. aureus, K. pneumoniae (CRE), K. pneumoniae, E. coli (CRE), E. coli, S. pneumoniae, E. faecalis, E. faecalis (VRE), E. faecium, A. baumannii, S. epidermidis, Methicillin resistant S. epidermidis, S. pyogenes, and Serratia marcescens are bound to the Seraph hemofilter's adsorption media as blood passes over it. This allows the concentration of bacteria in the bloodstream to be reduced by up to 85 percent in just a single pass of infected blood. Subsequent recirculation of the blood through Seraph results in a 3 to 4 log reduction in the level of pathogen in the blood in just a few hours. Reducing the patient's pathogen load in blood will lower the 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 certain pathogens and toxins that do not naturally bind to heparan sulfate. This group includes endotoxin, Pseudomonas aeruginosa, and Bacillus 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, thiswork has produced a growing body of peer reviewed published literature.
Defense Advanced Research Programs Agency (DARPA) - DLT
ExThera’s next generation device, Seraph 200* has been successfully evaluated in a collaborative research program with Battelle Memorial Institute, with the goal of developing a “Dialysis-Like Therapeutic” (DLT) intrinsic separation device to treat sepsis in wounded warriors In this program funded by a grant from DARPA, Seraph was the only device evaluated in the final phase of the competitive program, with other technologies having been down selected due to their inability to meet the program’s goals. Due to Seraph’s ability to quickly remove pathogens from a patient’s blood, DARPA regards the DLT program as having been a success.
*Seraph 200 is not CE Mark certified or commercially approved
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, especially within the first six months after beginning treatment, due to catheter-based blood access. (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 Medical’s clinical trials of Seraph in dialysis patients infected with bacteria, such as MRSA, S. aureus, K. pneumoniae (CRE), K. pneumoniae, E. coli (CRE), E. coli, S. pneumoniae, E. faecalis, E. faecalis (VRE), E. faecium, A. baumannii, S. epidermidis, Methicillin resistant S. epidermidis, S. pyogenes, and Serratia marcescens.
ExThera selected the hemodialysis patient population as its first group for clinical investigation in its European clinical trial. The company has received Expedited Access Pathway designation from the FDA. for treating patients with bacteremia, and is finalizing a protocol for treating patients with viremia. U.S. clinical trials are expected to begin 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.