A D V E R T I S E M E N T F E A T U R E

A D V E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y F O R C O N T E N T

Fibriant BVwww.fi briant.com

Nature-inspired recombinant hemostasis productsBiotech company Fibriant has developed a unique recombinant fibrinogen manufacturing platformthat is able to create a range of products that offer advantages over the plasma version.

Fibrinogen, a natural blood protein, is well known forplaying a key role in hemostasis, tissue repair andhost defence against pathogens. What is less widelyknown is that fibrinogen in human blood is actually amixture of variants, each with different functions andproperties that could be harnessed to improve exist-ing hemostatic applications or develop innovativemedical products in new therapeutic areas. However,extracting individual fibrinogen variants from humandonor plasma is commercially infeasible.

Fibriant, a biotech company based in Leiden, theNetherlands, has developed a unique recombinantfibrinogen manufacturing platform to take advan-tage of the many opportunities that fibrinogen vari-ants offer. Using industry standard CHO expressiontechnology and a purification process based on aproprietary affinity resin, the company is able toproduce specific human fibrinogen variants—fullyintact and functional—at commercially feasibleproduction levels and cost. And because fibrinogenis often used in combination with its physiologicalactivator thrombin, Fibriant has also developed arecombinant thrombin production process.

“Plasma versus recombinant fibrinogen is analo-gous to serum-derived polyclonal immunoglobu-lin versus recombinant monoclonal antibodies,”explained Jaap Koopman, Fibriant co-founder andCEO. “This is the first time in history that naturallyoccurring individual fibrinogen variants can be pro-duced in sufficient quantity for novel applications.”

Fibriant’s lead product, RecoSeel, is the first fullyrecombinant fibrin sealant for use as a biodegradableand bioactive topical haemostat to stop excessivebleeding during surgery. It is based on a fibrinogenvariant (selected for its optimal functional proper-ties) and recombinant thrombin (which converts sol-uble fibrinogen into an insoluble three-dimensionalfibrin matrix), and offers significant advantagesover plasma-derived topical haemostat products,a market worth $1.2 billion worldwide. “Recombinantthrombin is simply cheaper to produce as theamount in donor plasma is tenfold lower than ourrecombinant expression levels. And our recombinantfibrinogen is more stable as it is of high purity and notcontaminated with plasma proteases that degradethis large sensitive protein,” said Koopman. “Thisfacilitates the development of liquid formulationsof not only RecoSeel but also injectable fibrinogenproducts for use in acute bleeding situations.”

RecoSeel has demonstrated robust efficacy in pig-liver bleeding models, is expected to enter clinicaldevelopment in 2022, and has low developmentrisk as US Food and Drug Administration guidelinesare already available and Fibriant’s founders andtechnical staff have experience in developing topicalhemostat products.

Transforming natural variation intobespoke healthcare solutionsWhile plasma-derived fibrinogen is limited to topi-cal and injectable hemostat products, the health-care potential of recombinant fibrinogen is greater.

By focussing on specific variants, Fibriant canproduce customized products, such as specialtysealants and matrices, coatings and injectable con-centrates for use in wound closure, medical-implantbiocompatibility, and treating or preventing bloodloss (Fig. 1). Fibriant currently has four cell lines thateach produce a specific variant and is planning torecombinantly produce up to twelve variants thatare known to circulate in human blood.

A key area in Fibriant’s pipeline is host defence, witha focus on preventing and treating infections causedby methicillin-resistant Staphylococcus aureus (MRSA)bacteria. MRSA is known to hijack host proteins,especially circulating fibrinogen, to form biofilmson artificial surfaces or damaged tissue, enhancingits virulence and shielding the pathogen from hostimmunity and antibiotic treatment. However, one ofFibriant’s recombinant fibrinogen variants lacks theimportant pathogen-binding site; a proof-of-conceptstudy in mice demonstrated that pre-coating medicalimplants with this variant reduces biofilm formationand, importantly, increases sensitivity of the biofilm-associated MRSA bacteria to antibiotic treatment.

Tissue repair is another area of future application.“The fibrin matrix also facilitates tissue remodellingand regeneration by supporting cell migration andinfluencing cellular phenotype,” explained Koopman.“We aim to provide tailor-made recombinant fibrinmatrices with unique biochemical and biomechanicalproperties, for regenerative medicine applications.”

Partnering aspirationsFibriant is looking for investors and strategicpartners to help progress its pipeline and scale upGood Manufacturing Practice production of differ-ent fibrinogen variants and recombinant thrombin.The company is also keen to supply recombinantfibrinogen and/or thrombin as OEM products toother parties that would like to develop new prod-ucts or replace plasma proteins in existing products.

Recombinant production offers several advan-tages over plasma fractionation. Product consis-tency and safety is higher as the need for differentdonors is negated, avoiding the risk of blood-borndisease transmission. Furthermore, productioncapacity is virtually unlimited, is unaffected by pan-demics, such as COVID-19, or other global healthissues that threaten blood donation, and existingimport/export restrictions for plasma products donot apply, facilitating worldwide marketing.

“Individual fibrinogen variants, with their uniquestructure-function profiles, are an untapped health-care resource,” said Koopman. “We believe we are theonly company worldwide able to provide recombi-nant fibrinogen variants at commercially acceptablecost and maximise the value of this versatile moleculeinto customized hemostatic applications and innova-tive host-defence and tissue-repair products.”

Human fibrinogen variantsand human thrombin

Recombinant productionTissue repair

Tailor-madefibrin scaolds

Hemostasis

Injectablefibrinogen

Wound closure

Fibrin sealantsand glues

Infectiousdisease

Anti-bacterialbiofilm

coatings

OEM products

Otheruses

Replacement ofplasma products

Fig. 1 | Recombinant production platform for fibrinogen variants and thrombin. The platform enablesdevelopment of therapeutic end-products, as well as the supply of OEM products to companies who prefer touse recombinant fibrinogen and thrombin instead of plasma proteins. OEM, original equipment manufacturer.

Jaap Koopman, Chief Executive OfficerFibriant BVLeiden, the NetherlandsTel: +31 6 21 62 84 75E-mail: j.koopman@fibriant.com

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www.nature.com/biopharmdeal | March 2021 | B31