Our science
A Cell-Surface Target That Appears Only in Disease
Degradation of the extracellular matrix (ECM) drives cancer growth and chronic inflammation. Earlier attempts at this mechanism have foundered on selectivity, as their targets are also present on healthy tissue. Glycosylated Calnexin is different: it is a cell-surface target that has not been detected on healthy cells.
The GALA Pathway Moves Calnexin to the Cell Surface
Malignancy and chronic inflammation switch on GALNT Activation (GALA), a pathway that relocates glycosylation enzymes to the endoplasmic reticulum. There they O-glycosylate Calnexin, an ER chaperone, and translocate it to the cell surface.
At the surface, glycosylated Calnexin reduces the disulfide bonds that cross-link the ECM, initiating its degradation. Healthy cells do not switch the pathway on, so the surface form is a disease-activated target rather than a constitutive one.
Antibody blockade of the surface target inhibits this degradation. Genetically knocking out Calnexin stops it, and so does mutating its glycosylation sites, establishing glycosylated surface Calnexin as the critical driver of tissue degradation.
Published in Nature Cell Biology, 2020.
Driving Tumor Regression While Sparing Healthy Tissue
A solid tumor cannot grow or disseminate without dismantling the ECM around it. That matrix is the body’s physical barrier against metastasis, and metastatic disease accounts for the majority of cancer deaths.
Gastrointestinal tumors express glycosylated Calnexin at high levels. Our antibodies bind to the disease-activated surface target, internalize rapidly to the lysosome, and accumulate selectively in tumor tissue, reaching healthy organs at far lower levels.
Our antibody-drug conjugates (ADCs) have produced significant tumor regression in gastric, liver and bile duct cancers in preclinical models, with no detectable toxicity in vivo.
Preventing Cartilage Degradation in Arthritic Joints
Approved arthritis drugs target inflammatory signaling, not the degradation of cartilage. In osteoarthritis, no disease-modifying therapy is approved at all.
Activated synovial fibroblasts drive cartilage degradation in both rheumatoid arthritis and osteoarthritis, and they express glycosylated Calnexin. In preclinical models, the signal rises and falls with disease activity.
Our anti-Calnexin antibody protected cartilage in preclinical arthritis models, and inhibited more than 80% of ECM degradation by synovial fibroblasts isolated from arthritis patients.
Published in Nature Communications, 2025.
Preserving the Gut Wall in Inflammatory Bowel Disease
Degradation of the gut wall is what leads to perforation, bleeding and fistulae in IBD.
Glycosylated Calnexin is particularly elevated in Crohn’s disease and chronically inflamed colon. In a preclinical colitis model, our antibody reduced collagen degradation and preserved colonic crypt architecture.
Anti-TNFs, IL-23 inhibitors and JAK inhibitors all act on the immune system. Blocking Calnexin preserves the tissue directly, a mechanism no approved IBD therapy has.