Tonix Pharmaceuticals (TNXP) 2nd Richard Slayman Clinical Xenotransplantation Workshop presentation summary

Scientific background and rationale

• CD40L (CD154) is a transiently expressed surface protein on activated CD4+ T cells, crucial for T-helper function and antibody responses.

• Deficiency in CD40L leads to X-linked hyper-IgM syndrome, highlighting its role in immune regulation.

• The CD40-CD40L pathway is a validated target for immunomodulation in transplantation and autoimmune diseases.

Antibody engineering and generations

• First-generation anti-CD40L antibodies were effective but caused thromboembolic complications due to Fc receptor interactions.

• Second- and third-generation antibodies, including TNX-1500, were engineered to reduce FcγRIIa binding and minimize thrombosis risk.

• TNX-1500 retains the Fab of ruplizumab but features a selectively mutated Fc region to preserve efficacy and safety.

Preclinical and animal model data

• TNX-1500 monotherapy prevented kidney and heart transplant rejection in animal models, outperforming standard immunosuppressive regimens.

• No thrombosis was observed in preclinical studies, and TNX-1500 maintained effector function despite Fc modifications.

• TNX-1500 is being evaluated in non-human primate xenotransplantation models, showing promise for prolonged graft survival.