Kidney Week

Abstract: SA-PO644

Preclinical Safety and Scalability of VIS649 Production for Clinical Trials for the Treatment of IgA Nephropathy

Session Information

• Pharmacology
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Miller, Veronica M., Visterra, Inc., Waltham, Massachusetts, United States

Veronica M. Miller,

• Sloan, Susan E., Visterra, Inc., Waltham, Massachusetts, United States

Susan E. Sloan,

• Helger, Emily A., Visterra, Inc., Waltham, Massachusetts, United States

Emily A. Helger,

• Myette, James R., Visterra, Inc., Waltham, Massachusetts, United States

James R. Myette,

• Vollmer, Pat, Visterra, Inc., Waltham, Massachusetts, United States

Pat Vollmer,

• Szretter, Kristy J., Visterra, Inc., Waltham, Massachusetts, United States

Kristy J. Szretter,

• Deotale, Ketan, Visterra, Inc., Waltham, Massachusetts, United States

Ketan Deotale,

• Pereira, Brian J.G., Visterra, Inc., Waltham, Massachusetts, United States

Brian J.G. Pereira,

Background

IgA Nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, with no disease-specific therapies currently available. VIS649 is a humanized IgG2 monoclonal antibody targeting the cytokine named A Proliferation Inducing Ligand (APRIL) that is implicated in the pathophysiology of IgAN. To demonstrate the feasibility of generating a commercially available VIS649 treatment, the preclinical effects, potency and safety attributes of VIS649 materials that were produced using a range of scaled down bench-top and scaled up manufacturing processes were compared.

Methods

VIS649 was first produced in-house using a CHO cell line – Batch 1, followed by small scale production at a CRO using a pool of CHO clones (Batch 2) and finally at a larger-scale manufacturing plant using CHO cells from a research cell bank (Batch 3). Each batch of VIS649 was then assessed for preclinical safety and efficacy in non-human primates (NHPs). In addition, in vitro analytical assays were used to compare the batches including APRIL binding (ELISA), and engagement with immune factors and receptors (complement, FcRI, FcRII and FcRIII binding by Octet). Finally, because glycans can influence the half-life and metabolism of immunoglobulins the glycan profile of each batch was assessed using MS, HPLC and CE methods.

Results

VIS649 synthesized at each scale was found to produce equivalent maximal reductions in circulating IgA levels (~70%) in the NHP studies. Furthermore, in vitro assessments confirmed that the three batches of VIS649 had similar binding to APRIL, as well as minimal FcRI, II, III and complement binding. Observed minor changes in glycans were not found to impact in vivo or in vitro VIS649 activity.

Conclusion

These data confirm that VIS649 production can be consistently scaled from small to larger scale manufacturing, while retaining important potency, purity and safety characteristics. These results support that large-scale production of VIS649 will be suitable for use in clinical trials to assess both safety and efficacy in IgAN patients.

Funding

• Commercial Support –