Abstract: FR-PO795
Tegoprubart Reduced Inflammation in Patients With Amyotrophic Lateral Sclerosis (ALS): Potential Implications for Its Use in the Prevention of Rejection in Kidney Transplant
Session Information
- Transplantation: Clinical - Biomarkers
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Perrin, Steven, Eledon Pharmaceuticals, Irvine, California, United States
- Gill, Alan, ALS Therapeutic Discovery Institute, Boston, Massachusetts, United States
- Bornstein, Jeffrey D., Eledon Pharmaceuticals, Irvine, California, United States
- Theilhaber, Joachim, Eledon Pharmaceuticals, Irvine, California, United States
Background
Tegoprubart (AT-1501) is a monoclonal antibody that inhibits CD40 ligand (CD40L); it is expected to downregulate both cell mediated and antibody mediated immunity while also creating a more tolerogenic environment, and preventing antibody class switching, reducing high affinity IgG antibodies. Tegoprubart is currently being evaluated in an ongoing trial in kidney transplant (KT).
Methods
Tegoprubart was studied in an open-label, dose-escalating trial in patients with ALS. 54 participants received tegoprubart at doses of 1mg/kg (N=9), 2mg/kg (N=9), 4mg/kg (N=18) or 8mg/kg (N=18) IV every 2 weeks for 6 infusions. Safety and the effect of tegoprubart on inflammatory biomarkers were assessed. Target engagement was measured directly via reduction in CD40L and indirectly using CXCL13, a marker of B cell activation. Pro-inflammatory chemokines and cytokines previously shown to be elevated in ALS patients were assessed, and several of these biomarkers may be relevant to the ongoing studies in KT, notably CXCL9 and CXCL10.
Results
Tegoprubart appeared safe and well tolerated at the doses administered. Target engagement was achieved in a dose dependent fashion. In this population of ALS patients, tegoprubart reduced inflammatory biomarkers with the same dose dependent pattern as target engagement. Importantly for KT, tegoprubart reduced CXCL9 and CXCL10, chemokines reported to be associated with acute allograft rejection.
Conclusion
In a study of patients with ALS, tegoprubart at doses of 4mg/kg and 8mg/kg IV every 2 weeks demonstrated target engagement with an associated reduction in inflammation. Among the inflammatory biomarkers reduced were CXCL9 and CXCL10, positive signals for tegoprubart's ongoing program in KT.
Funding
- Commercial Support –