Genovis AB and Selecta Biosciences, Inc. announced strategic licensing agreement to advance a next-generation IgG protease. This partnership leverages Genovis' proprietary immunoglobulin G (IgG) protease, Xork, and Selecta's ImmTOR platform to enable the dosing of transformative gene therapies in patients with pre-existing adeno-associated virus (AAV) immunity and treat certain IgG-mediated autoimmune diseases. Most IgG proteases are derived from human pathogens and have a high prevalence of pre-existing antibodies.

Xork is derived from a streptococcal bacterial strain that does not infect humans. The pre-clinical data generated to date highlights Xork's differentiated profile - demonstrating very low cross-reactivity with naturally occurring antibodies in human sera while retaining efficient and specific cleavage of human IgG antibodies. Currently, pre-existing IgG antibodies against AAV gene therapy vectors are a major exclusion criterion for AAV gene therapy eligibility, affecting upwards of 40% of the population.

Additionally, de novo immunogenicity that follows treatment by AAV gene therapy results in the formation of high titers of neutralizing antibodies. These neutralizing antibodies preclude re-treatment of those patients who may need additional dosing to maintain therapeutic benefit. The combination of Xork and ImmTOR has the potential to both mitigate pre-existing antibodies to AAV, expanding access to gene therapy to a wider range of patients, and prevent de novo immunogenicity, keeping patients eligible for re-treatment.

Together, this novel combination has the potential to address two of the key hurdles in gene therapy today. Additionally, bacterial-derived IgG proteases are themselves immunogenic. Currently, IgG proteases can only be administered once due to the formation of high titer antibodies against the protease itself.

The combination of Xork and ImmTOR is further differentiated by the potential of ImmTOR to mitigate the immunogenicity of Xork and enable re-dosing of Xork, an important benefit for the application of IgG proteases in autoimmune diseases mediated by pathogenic autoantibodies.