VPI-2690B is a first-in-class subcutaneously (under the skin) administered monoclonal antibody with a unique mechanism of action. Monoclonal antibodies are laboratory-produced molecules that mimic the immune system's naturally produced antibodies. VPI-2690B binds to a very specific target in the kidney, the C-loop domain sequence within a cell's αVß3 receptor. This receptor plays a role in the insulin-like growth factor-I (IGF-I) signaling pathway. Because αVß3 is expressed on multiple types of kidney cells (podocytes, endothelial and mesangial cells) it is ideal for monoclonal antibody targeting.
In diabetes, high glucose levels cause an increase in αVß3 ligands (or binding molecules) and stimulate abnormal αVß3 activation. This over activation signals cellular changes that break down filtering capability and decrease kidney function. VPI-2690B prevents these ligands from binding, which normalizes the signaling process and prevents cellular changes. This stops further kidney damage from occurring and may also result in damage reversal.
Animal studies in a diabetic pig model with VPI-2690B showed a significant improvement in cellular changes such as glomerular basement membrane thickening and podocyte effacement. The key indicator of damaged kidney filtration—protein in the urine—was also normalized following treatment. To date, Vascular Pharmaceuticals has completed an ascending single/multiple dose Phase 1 study of VPI-2690B in healthy volunteers. The results showed that the drug is safe with significant levels of drug exposure and exhibited a consistent, predictable safety profile. A Phase 2 clinical trial is currently ongoing and is enrolling new patients.