PIPELINE

VIS649 for Immunoglobulin A Nephropathy (IgAN)
VIS649
Our first product candidate outside of infectious diseases, VIS649, is a monoclonal antibody, or mAb, for the treatment of Imumuglobulin A Nephropathy, or IgAN. IgAN is the most common cause of primary kidney disease worldwide. IgAN is associated with kidney inflammation, blood in the urine, or hematuria, and protein in the urine, or proteinuria. Patients ultimately progress to end-stage kidney disease and require dialysis or kidney transplantation in 20%-40% of cases over 20 years after diagnosis. IgAN is an autoimmune disease wherein a respiratory or gastrointestinal mucosal infection in susceptible individuals can lead to production of an abnormal form of IgA called aberrantly glycosylated IgA, or “a-g” IgA. Unlike normal IgA, “a-g” IgA induces the production of antibodies and results in the formation of disease-causing immune complexes. These immune complexes get deposited in the kidney and lead to kidney inflammation, hematuria, proteinuria and progressive kidney damage. Third-party studies have shown that “a-g” IgA levels in plasma are elevated in patients with IgAN compared to healthy individuals, and higher plasma levels of “a-g” IgA are associated with faster progression to kidney failure. The cell signaling molecule, or cytokine, A Proliferation Inducing Ligand, or APRIL, has emerged in the scientific literature as a key factor in the pathogenesis of IgAN. Currently, there is no specifically approved therapy for IgAN.

We have used our platform to identify the Hierotope on APRIL to target, and have designed and engineered a mAb, VIS649, to bind to this Hierotope and neutralize the biological activity of APRIL. We believe that the Hierotope targeted by VIS649 is distinct from epitopes targeted by other anti-APRIL antibodies that are being developed by other companies. In our preclinical studies in cell culture systems, VIS649 exhibited potent inhibition of APRIL interactions with both its receptors: Transmembrane Activator and CAML Interactor, or TACI, and B-Cell Maturation Antigen, or BCMA. We have engineered VIS649 as an antibody that does not bind to and activate complement, which is an undesirable property in kidney diseases because complement deposition in the kidney can worsen kidney disease. We plan to initiate Phase 1 clinical trials of VIS649 in 2018 and to request orphan drug designation from the FDA and EMA for VIS649 for the treatment of IgAN.

About IgA Nephropathy
Diseases that solely manifest in the filtering component of the kidney are called primary glomerular diseases, and IgAN is the most common cause of primary glomerular disease worldwide. The annual incidence rate of IgAN has been estimated in scientific literature to be 25 cases per million individuals worldwide, with a higher incidence in Eastern Asian populations and lower incidence in African populations. In the United States, the annual incidence is estimated to be approximately 10 cases per million individuals. Based on these incidence rates, we estimate that there are approximately 3,200 new cases of IgAN in the United States each year and approximately 185,000 worldwide. IgAN is associated with kidney inflammation, hematuria and proteinuria. Patients ultimately progress to kidney failure or end-stage kidney disease and require dialysis or kidney transplantation in 20%-40% of cases over 20 years after diagnosis. IgAN commonly recurs after kidney transplantation. Kidney function is measured by the glomerular filtration rate, or GFR, and is normally 90 ml to 120 ml per minute in adults with a body surface area of 1.73 square meters, or 125 ml/1.73 m2. End-stage kidney disease is characterized by a GFR <15 ml/1.73 m2.

IgAN is an autoimmune disease wherein a respiratory or gastrointestinal mucosal infection in susceptible individuals can lead to production of “a-g” IgA, an abnormal form of IgA. Unlike normal IgA, “a-g” IgA induces the production of antibodies and results in the formation of disease causing immune complexes. These immune complexes get deposited in the kidney and lead to kidney inflammation, hematuria, proteinuria and progressive kidney damage. Third-party studies have shown that “a-g” IgA levels in serum are elevated in patients with IgAN compared to healthy individuals, and higher serum levels of “a-g” IgA are associated with faster progression to kidney failure. The cytokine APRIL has emerged in the scientific literature as key factor in the pathogenesis of IgAN. APRIL has a physiological role in IgA production, and plasma levels of APRIL have been shown to correlate directly with plasma levels of “a-g” IgA. Based on third-party studies, patients with IgAN have increased production of APRIL, as compared to healthy individuals, which leads to elevated APRIL plasma levels, and higher plasma levels of APRIL are associated with faster progression to kidney failure. Furthermore, as described in a peer-reviewed scientific journal, in a study in a mouse model of IgAN, administration of an anti-APRIL antibody protected against worsening of proteinuria and demonstrated reduction of the IgA deposits in the kidney. For these reasons, we believe APRIL may be an attractive target for the treatment of IgAN.


As of 09/15/17

Visterra, Inc. | One Kendall Square, Suite B3301 | Cambridge, MA 02139 | 617-498-1070 | © 2017 Visterra, Inc. All Rights Reserved.