Selecta and Genovis Enter License Agreement to Advance Next-Generation IgG Protease in Gene Therapy and Autoimmune Disease

Selecta Biosciences and Genovis said they have entered into a strategic licensing agreement to leverage their technologies to enable the dosing of transformative gene therapies in patients with pre-existing adeno-associated virus immunity and treat certain IgG-mediated autoimmune diseases.

Selecta uses its ImmTOR platform to develop gene therapies that selectively mitigate unwanted immune responses and Genovis is advancing a next-generation IgG protease, IdeXork (Xork), which can address pre-existing neutralizing antibodies.

Under the terms of the agreement, Selecta has provided Genovis with an upfront payment for an exclusive license to Xork for all therapeutic uses in humans while Genovis retains rights to research, preclinical, diagnostic, and other potential non-therapeutic applications of Xork. Additionally, Genovis is eligible to earn development and sales-based milestones, as well as tiered royalties on worldwide sales in the low double digits.

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 demonstrates 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 percent 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 companies said that 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.

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.

“The partnership between Selecta and Genovis focuses on those patients who would otherwise be unable to be treated due to pre-existing immunity to AAV,” said Carsten Brunn, president and CEO of Selecta. “The combination of ImmTOR with Xork has the potential to significantly expand access to life changing gene therapies for those patients in need.”