Martin Dahl, PhD: Rosnilimab Demonstrates Favorable Safety, Pharmacokinetics in Healthy Patients

In an interview with HCPLive, Martin Dahl, PhD, senior vice president of research at AnaptysBio, discussed the results of his study, “Rosnilimab, a Novel PD-1 Agonist Monoclonal Antibody, Inhibits Peripheral T Cell Proliferation and Cytokine Secretion and Reduces Circulating PD-1 High Expressing CD4 and CD8 T Cells: Results from a Phase 1 Healthy Volunteer Clinical Trial,” presented at the American College of Rheumatology’s 2023 Convergence in San Diego, California.¹

Motivated by an unmet need in rheumatoid arthritis (RA), the study sought to investigate rosnilimab's dual mechanisms of action: the depletion of PD-1 high T cells and the agonism of PD-1 positive T cells.

The decision to evaluate rosnilimab through a phase 1 healthy volunteer study adheres to standard drug development protocols, prioritizing patient safety. Beyond safety assessments, the study aimed to enhance the understanding of the drug's pharmacokinetics and pharmacodynamics, particularly regarding half-life and its impact on PD-1 high T cells.

The inspiration stems from real-world studies revealing persistent challenges in achieving RA remission with current therapies. The study's key findings indicate rosnilimab is well tolerated, an absence of safety concerns, and a dose-dependent reduction in peripheral PD-1 positive T cells. There was a potent and sustained reduction in peripheral PD-1+ T cells for more than 30 days, supporting its potential for monthly dosing.  Importantly, the study shows rosnilimab's specificity in targeting PD-1 positive T cells, especially the PD-1 high T cells prevalent in inflamed tissues.

Dahl explained the results are significant in the context of RA, where these T cells play a crucial role in pathogenesis. The next steps involve advancing to a global phase 2 study in moderate to severe RA patients, building on the promising phase 1 data. A phase 2 study in ulcerative colitis is also planned, where there is evidence of PD-1 positive T cell enrichment in the colon. The optimization of rosnilimab's specific activity for maximal PD-1 agonism and depletion properties, based on a membrane-proximal epitope, adds to its potential efficacy and safety.

Dahl stated the anticipation is high for phase 2 data in RA and ulcerative colitis, marking a decade-long journey in studying checkpoint agonists.

References

1. ^{Luu K, Dahl M, Hare E, Sibley C, et al. Rosnilimab, a Novel PD-1 Agonist Monoclonal Antibody, Inhibits Peripheral T Cell Proliferation and Cytokine Secretion and Reduces Circulating PD-1 High Expressing CD4 and CD8 T Cells: Results from a Phase 1 Healthy Volunteer Clinical Trial. Presented at: American College of Rheumatology Convergence 2023. San Diego, CA. November 10-15, 2023.}