THERAPEUTIC ANTIBODIES NEUTRALIZING ALL THE ORTHOPOXVIRUS INFECTIOUS FOR HUMANS, INCLUDING SMALLPOX

ArAv87 is a broad-spectrum, human-like, anti-L1, recombinant antibody, developed by IRBA, that neutralizes in vitro the four orthopoxvirus infectious for humans. In the plaque reduction assay, the IC50 values of ArAv87 are 83.9ng·mL⁻¹ for vaccinia virus, below 18.5 ng·mL⁻¹ for cowpox virus, 20 ng·mL⁻¹ for monkeypox virus and 1 ng·mL⁻¹ for variola major virus. Currently, there is no specific therapy for orthopoxvirus infections, that can be produced and used in a large scale. Therefore, ArAv87 antibody is a promising broad-spectrum molecule for the prevention and the therapy of diseases induced by orthopoxvirus, in a natural (pandemic) or intentional (bioterrorist or biowarfare attack) context. In THANATOS, ArAv87 will be optimized to increase its affinity, its clinical tolerance, its manufacturability and its stability. An original and efficient approach combining artificial intelligence and gold-standard conventional techniques of laboratory will be used to realize this optimization with a very limited time and funds. Optimized ArAv87 antibody will be tested in vivo against mpox in mice and non-human primate model. Then, the preclinical development of optimized ArAv87 will be realized, to guaranty the safety and efficacy of the antibody before the first-in-human study. After the production under GMP conditions, the clinical safety of this antibody will be evaluated in a clinical trial phase 1 in cohorts of healthy volunteers.