Dual BAFF/APRIL B cell cytokine antagonist with best-in-class potential

ALPN-303 is a dual B cell cytokine antagonist being developed for multiple autoimmune and inflammatory diseases.

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 filingscorporate presentation, and scientific publications.

ALPN-303: Engineered Inhibitor of BAFF (BLyS) and APRIL
Clinically-Validated B cell Modulatory Pathways
ALPN-303 Exhibits Encouraging Efficacy in Murine Connective Tissue Disease
ALPN-303 inhibits the activity of the B cell cytokines APRIL and BAFF more potently than
wild-type TACI-Fc counterparts, as well as anti-BAFF and anti-APRIL monoclonal antibodies

Join us in the discovery and development of next-generation immunotherapies.

Current job openingsLearn more about Alpine