Reduction of Pathogens in the Bloodstream

Seraph® 100 Microbind® Affinity Blood Filter

Clinical Use of Seraph 100

The Seraph 100 is a therapy that reduces SARS-CoV-2 and other pathogens in the blood. It is indicated

under CE Mark for the reduction of pathogens in the bloodstream in adjunction to antibiotic treatment during

bloodstream infections1 and is available in the US under FDA Emergency Use Authorization for the Treatment

of COVID-192. In vivo and in vitro studies have confirmed the reduction of various pathogens like methicillin-

resistant Staphylococcus aureus (MRSA)3,4, SARS-CoV-2 virus5,6,7,8 in the blood.

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• Mortality was much lower in the Seraph 100 treated group compared to the matched controls: 37.7% vs. 67.4% respectively (p=0.003)9

• Multivariate logistic regression analysis yielded an odds ratio of 0.27 (95% confidence interval 0.09- 0.79, p=0.016): Nearly 4X improvement in survivability odds when severely ill COVID-19 patients are treated with Seraph 1009

• These results support the 2021 launch of a US multicenter randomized controlled feasibility trial of the Seraph 100 for septic shock due to any pathogen9

• Another study’s preliminary results demonstrated 73% survival with Seraph 100 use compared to 27% non-Seraph 100 use10

Preliminary Observed Outcome Results Are Promising: PURIFY OBS & COSA Registry

Seraph 100 Product Benefits

• Broad-spectrum pathogen-binding capability of proprietary endpoint-attached heparin6,11

• Negligible removal of 22 common anti-infective drugs, including Remdesivir, while there was a relevant initial adsorption of 2 aminoglycosides.12,13,14,15

• Only product commercially available with the indication: Bloodstream pathogen reduction (CE Mark indication only)

• Broad-spectrum binding of gram-negative and gram-positive bacteria as well as viruses6

and fungi

• May make early initiation reasonable without awaiting pathogen identification

• Endpoint-attached heparin is anti-thrombogenic and anti-inflammatory11

• Compatible with most RRT/ hemoperfusion machines

• Safety profile consistent with standard extracoproreal labeling

Ongoing Clinical Research

• Pathogen associated shock multicenter randomized controlled trial.

• Blood Purification With Seraph 100 Microbind Affinity Blood Filter for Treatment of Severe COVID-19 Observational Study (PURIFY-OBS-1)

• Reduction of Pathogen Load From the Blood in Septic Patients With Suspected, Life-threatening Bloodstream Infection

• Registry of COVID-19 Patients Treated With the Seraph 100 Microbind Affinity Blood Filter (COSA)

• Registry of Seraph® 100 Microbind® Affinity Blood Filter for COVID-19 Under EUA

Mechanism of Action

Why Seraph 100?Compared to other hemopurification filters, the Seraph

100 pathogen adsorption mechanism significantly

differs from cytokine or endotoxin adsorption. Therapy

is delivered earlier in the patient journey during

bacteremia/viremia/fungaemia (pathogens in the

blood), where traditional blood purification techniques

adsorb mediators after cascading illness adsorb

mediators later, after cascading illness.

Treating COVID-19 Variants with Seraph 100

Most COVID mutations occur outside of their heparin

binding site18 enabling Seraph to continue binding

COVID variants beyond the original strain.

The Endothelial Glycocalyx • The glycocalyx is an endothelial matrix lining the

vascular endothelium and its key constituents include glycoproteins, proteoglycans and glycosaminoglycans.

• The glycocalyx provides multiple functions, including the regulation of vascular permeability.16

• Many viruses and bacteria can bind to cell surface heparan sulfate proteoglycans, which facilitates initial pathogen attachment and promotes infection.17

The Seraph 100 - A Surrogate Glycocalyx

• The microbead broad-spectrum adsorption media of Seraph 100 use chemically bonded heparin to mimic the natural endothelial cell surface.

• This resembles the glycocalyx with its heparan sulfate content and can be expected to bind pathogens circulating in the bloodstream.6

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Cross-sectional blood vessel with the glycocalyx16

Binding mechanism of heparin/heparan sulfate

Seraph ® 100 microbeads with blood cells

EG: Endothelial glycocalyx, EC: Endothelial cells

*

Heparan sulfate

Surface of non-porous Seraph media

Cell surface

Toxin

Peptide backbone

PathogenHeparin/Heparan sulfate bind:- Bacteria- Viruses

- Toxins- Cytokines

- ATII

ATIII

ATIII

ATIIIATIII

Heparin

REFERENCES

1. Seraph 100 Microbind Affinity Blood Filter Instructions For Use: CP009 Rev C

2. Seraph 100 Microbind Affinity Blood Filter Instructions For Use, US Emergency Use Authorization: CP021 Rev A

3. Mattsby-Baltzer et al., Affinity Apheresis for Treatment of Bacteremia Caused by Staphylococcus aureus and /or Methicillin-Resistant S. aureus (MRSA) J. Microbiol. Biotechnol. (2011), 21(6), 659 – 664

4. Seffer et al, Elimination of Staphylococcus aureus from the bloodstream using a novel biomimetic sorbent haemop…, BMJ Case Studies (2020); 13(8)

5. Olson et al, Treatment for Sever Coronavirus Disease 2019 With the Seraph-100 Microbind Affinity Blood Filter (2020); 2(8), 1-6

6. Seffer et al, Heparin 2.0: A New Approach to the Infection Crisis, Blood Purification (2020); Jul 2, 1-7

7. McCrea et al, Removal of Cytomegalovirus from blood by Heparin- functional Hemoperfusion Media (abstract), SCCM (2015); 2411

8. Kielstein et al, Hemofiltration with the Seraph® 100 Microbind® Affinity filter decreases SARS-CoV-2 nucleocapsid protein in critically ill COVID-19 patients. Crit Care. 2021 Jun 1;25(1):190.

9. Chitty et al, A Multicenter Evaluation of Blood Purification with Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19: A Preliminary Report, (2021);

Technical Data: Seraph® 100

10. Schmidt et al, First results of the COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter (COSA) registry, AKI & CRRT 2021, 176-178, Abstract

11. McCrea et al, Removal of Carbapenem-Resistant Enterobacteriaceae (CRE) from Blood by Heparin-Functional Hemoperf…, PLOS One (2014); 9(12)

12. Schmidt et al, In vitro elimination of anti-infective drugs by the Seraph® 100 Microbind® affinity blood filter, CKJ (2020); 13(3), 421-424

13. Seffer et al, Clearance of chloroquine and hydroxychloroquine by the Seraph® 100 Microbinda Affinity Blood Filter -a device approved for the treatment of COVID-19 patients. Ther Apher Dial. 2021 Apr;25(2):237-241.

14. de Geus et al, The Seraph®-100 Microbind Affinity Blood Filter Does Not Affect Vancomycin, Tacrolimus, and Mycophenolic Acid Plasma Concentrations. Blood Purif 2021.

15. Schmidt, J., et. al. “Pharmacokinetics of Remdesivir and GS-441524 during PIRRT and Seraph 100 Therapy”, CJASN, accepted for publication.

16. Biddle C. Like a slippery fish, a little slime is a good thing: the glycocalyx revealed. AANA J. 2013 Dec;81(6):473-80. PMID: 24597010

17. Bartlett et al, Heparan Sulfate Proteoglycans in Infection, in: Pavao M. (eds) Glycans in Diseases and Therapeutics. Biology of Extracellular Matrix. Springer, 2011

18. Gupta et al, Heparin: A simplistic repurposing to prevent SARSCoV-2 transmission in light of its in-vitro nanomolar efficacy. Int J Biol Macromol. 2021 Jul 31;183:203-212.

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L40123 Rev. C

Extracorporeal Volume 160 mL

Typical Blood Flow Rate 100 – 350 mL/min

Max. Treatment Duration 4 ± 1 hours

Shelf Life 3 years

Dimensions Ø 7.6 x 23 cm

Bead Diameter ~300 µm

Surface Area 40 m²

Setup Time ~5 minutes

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