On October 21, 2021 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, and Genovis (GENO), an enzyme technology company, reported a strategic licensing agreement to advance a next-generation IgG protease (Press release, Selecta Biosciences, OCT 21, 2021, View Source [SID1234591674]). This partnership leverages Genovis’ proprietary immunoglobulin G (IgG) protease, IdeXork (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.

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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.

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.

Fredrik Olsson, chief executive officer of Genovis, commented, "We are excited to partner with Selecta as we look to expand into the gene therapy field and address the challenge of pre-existing immunity to AAV vectors. While IgG proteases have shown promise, overcoming the immunogenicity of the enzyme remains a significant hurdle. We believe Selecta’s ImmTOR platform, which is designed to mitigate unwanted immune responses, in combination with Xork has the potential to be transformational in both gene therapies and autoimmune diseases."

"We see this strategic collaboration with Genovis as an important step in expanding our pipeline of novel therapeutics in combination with our ImmTOR platform," said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. "Our preclinical findings in gene therapy indicate that ImmTOR has the potential to increase transgene expression and durability, enable re-dosing by inhibiting the formation of neutralizing antibodies and potentially lead to safer, more efficacious gene therapy treatment regimens. 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. The combination of ImmTOR with Xork has the potential to significantly expand access to life changing gene therapies for those patients in need."

Terms of agreement
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.