EPIC CROWN 2 Equine Polyclonal antibodies Immunotherapy against COVID-19/SARS-CoV2–VOC

In the absence of approved specific antiviral therapies for vaccinated-non-responders and the scarce anti-inflammatory therapies, passive immunotherapies with polyclonal immunoglobulins could be considered a part of the solution.


The main objective of EPIC-CROWN-2 is to rapidly assess, in multicentric clinical trials, an EMA-authorized antiviral immunotherapy based on potent and broad equine neutralizing anti-SARS-CoV-2 polyclonal F(ab’)2 antibodies in COVID-19 patients, including VOC carriers. In order to save lives and reduce the use and costs of critical care, this therapeutic solution is expected to reduce at least by 50% ICUs admissions and a highly significant mortality rate of treated patients.


To optimize the indications for the treatment, potency and breath of F(ab’)2 against variants will be assessed in in vitro and in an animal model as well as prospective studies will respectively be done on immune assessment in treated patients and on mitigation of exacerbated immune responses in vivo.


Fab’entech will coordinate EPIC-CROWN-2 formed by outstanding experts in different project domains that include clinical trials (HISS, Greece), virology (IMAS12, Spain), and immunopathology models and mitigation (BNITM, Germany - IRD, France). Most of them having already been working together in European projects. Importantly, EPIC CROWN 2 will be integrated as part of both the large European trial network EU-RESPONSE and the multinational European Adaptive Platform Trial “Solid Act".


With these studies EPIC-CROWN-2 shows completeness for three main reasons: (i) the phase IIa study that will provide all necessary information on pharmacokinetics and safety; (ii) the phase IIb study that will provide the safety and efficacy of FBR-002 in the clinical practice. To this end, the phase IIb study is comprising one double-blind randomized design and aims to demonstrate how early start of treatment with FBR-002 may prevent progression of severe respiratory failure, which is the most threatening complication of COVID-19; (iii) In the same aspect EPIC-CROWN-2 is also trying to provide one robust response to the question whether FBR-002 is showing clinical benefit when administered to patients irrespective of the variant of SARS-CoV-2.


Objective 2: To analyse the impact of SARS-CoV-2 VOC within clinical batches of polyclonal F(ab’)2 (FBR-002) antibodies by in vitro and in vivo studies.


Circulation of SARS-CoV-2 variants has raised concerns, since changes on the spike protein and specially in the receptor-binding domain (RBD) region are associated with an increased transmissibility and can also determine immune escape to neutralizing antibodies induced by natural infection or vaccination. New appearance of VOCs is expected in the context of high pandemic activity as it has been the case in South Africa were the new VOC “Omicron” (B.1.617) has been recently described, which was then rapidly detected in several European countries. The impact of VOCs on new therapeutics is largely unknown and a number of monoclonal antibodies have been rendered inactive against this latest VOC.

A polyclonal approach targeting multiple epitopes could more easily counteract the scape properties of specific mutations. We have aimed to investigate the neutralizing magnitude and breadth against circulating and future VOC of clinical batches of FBR-002 antibodies both in vitro and an in vivo model of SARS-CoV-2 infection.


Objective 3: Prospective clinical and in vivo studies to improve the indications of the treatment.


Considering that the main scope of this project is to assess an EMA-authorized anti-SARS-CoV-2 immunotherapeutic approach based upon clinical GMP batches of potent and broad horse polyclonal anti-SARS-CoV-2 F(ab’)2 antibodies in COVID-19 patients infected by VOC, it is important to assess beneficial impacts of this treatment that obviously will depend on the patient’s inclusion criteria, administration route and dosage. To optimize the therapeutic indications, one of the key aspects are the inclusion criteria. Among these criteria, immune status is one of the most important, since they depend on general health status of patients exhibiting or not co-morbidities or particular genetic characteristics. To contribute to accurately assess the impact of the treatment, the clinicians will assess the general health status (the most important criteria) of FBR-002-treated patients to accurately provide clinical data on the determined endpoints of efficacy.

We propose to complete these clinical observations with prospective studies on (i) the assessment of the clinical evolution of virological and immune parameters (innate and adaptive) before and after the FBR-002 treatment in patients and (ii) the characterization of some possible biomarkers that could prospectively help to both accurately assess the impact of the FBR-002 treatment beyond the general health status, as well as to prospectively define the inclusion criteria, which will help to optimize the indications for this treatment.

In addition, prospective in vitro (IRD) and in vivo (small animal model at BNITM) experiments will be done to fine-tune patented lead compounds (issued from biomarkers studied) that have already shown critical protective effects on exacerbated loss of the integrity and function of endothelial and epithelial barriers. If a clear in vivo efficacy proof of concept is done, therefore clinical studies could be then proposed with these compounds. Ultimately, these compounds could be as one tier for potential combined mitigation of ARDS in severe COVID-19.


Objective 4: Preparation of the market uptake to timely access to GMP production to be trialled and strategy definition for the upscale production.


This objective runs along two main axes:

  • The consolidation of the exploitation plan including production upscaling, regulatory and marketing strategy to address the market in the different outbreak scenarios (new peaks, seasonal outbreak, outbreak disappears);
  • Raise awareness and prepare for uptake of the EPIC-CROWN-2 solution by disseminating and engaging with the scientific community, practitioner community, Key Opinion Leaders (KOL) and decision-makers.


To ensure and maximise the impact, the EPIC-CROWN-2 project has developed a concrete and feasible plan for the industrial production and scale-up of FBR-002 production. This plan will enable a step-by-step implementation depending on public health needs in terms of treatment as well as the capacity to finance it.

The FAB production facilities of highly-purified specific large-scale production of F(ab’)2 immunotherapy using already available antigens (since July 2020) enables fast deployment and scale-up of the anti-COVID-19 immunotherapy solution developed in the project.

video / video

partners / contact


[ FAB ]


Anaïs Belledant

Anaïs Belledant


[ IRD ]


Francisco Veas

Francisco Veas

Instituto de Investigación 12 de Octubre

[ IMAS12 ]


Rafael Delgado

Rafael Delgado

Hellenic Institute for the Study of Sepsis

[ HISS ]









This project has received funding from the European Union’s Horizon Europe research and innovation programme under grant agreement No 101046084. This publication [communication] reflects the views only of the author, and the Commission cannot be held responsible for any use which may be made of the information contained therein.

graph - chart

Start 01/06/2021
End 30/11/2023
Budget allocation . M€ Budget allocation
Effort 412 p*m Effort
Effort 14 persons Full time equivalent


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