ALPN-303
Dual BAFF/APRIL B cell cytokine antagonist with best-in-class potential
Engineered by directed evolution of the extracellular domain of the TACI receptor, ALPN-303 potently inhibits the pleiotropic B cell cytokines B cell activating factor (BAFF, BLyS) and a proliferation inducing ligand (APRIL), which play key roles in B cell development, differentiation, and survival, and together contribute to the pathogenesis of B cell-related autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren’s syndrome, inflammatory arthritis, multiple sclerosis, and other conditions. By simultaneously blocking these two cytokines, ALPN-303 has the potential to improve clinical outcomes in patients suffering from severe inflammatory/autoimmune diseases.
The potential best-in-class potential of ALPN-303 is supported by research presented at the 2021 ACR Virtual Annual Meeting demonstrating that compared to wild-type TACI-Fc:
- ALPN-303 inhibits the activity of the B cell cytokines APRIL and BAFF with greater than fivefold potency in vitro;
- In mice, ALPN-303 exhibits superior pharmacodynamics, including greater suppression of T-dependent antibody production and reduction of B cell populations, such as follicular B cells;
- In cynomolgus monkeys, ALPN-303 is well tolerated and exhibits nearly threefold greater serum exposure, accompanied by a greater than 2.5X maximal percent reduction from baseline in serum immunoglobulins (IgG, IgM, IgA); and
- In a mouse model of lupus, ALPN-303 treatment significantly suppresses anti-double stranded DNA antibody titers, and inflammation in the kidneys (glomerulonephritis), while preserving renal function and improving survival.
We are currently enrolling patients in a Phase 1 healthy volunteer study. For more information on our ongoing clinical trials please refer to the clinical trials portion of our website.
For additional information please refer to our corporate filings, corporate presentation, and scientific publications.