In inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, there remains a significant unmet medical need for agents that have a rapid onset of action, attain mucosal healing and are non-immunosupressive. In the United States alone, it is estimated that there are approximately 800,000 adults diagnosed with moderate-to-severe IBD¹. Immune suppressants and anti-inflammatory biologics can be effective treatment options for people with IBD, however many do not achieve adequate long lasting disease control nor histological remission, which is considered a treatment target and may be associated with a reduction in need for hospitalization and colectomy (Magro et al. 2020 ECCO Position Paper: Harmonisation of the approach to Ulcerative Colitis Histopathology). We believe that there remains considerable unmet need to achieve histological remission by directly addressing epithelial damage in moderate to severe disease.
Wnt/β-catenin signal plays an important role in intestinal epithelium homeostasis and injury repair. There is a strong physiological Wnt signal that stimulates Lgr5+ stem cells, functional turnover, and differentiation of the intestinal epithelium. In IBD, Wnt signaling is deregulated resulting in a loss of normal epithelial architecture, and a loss of mucosal integrity. By restoring Wnt signaling with a therapeutic molecule, the intestinal epithelium can be repaired and the barrier function restored, complementing currently approved anti-inflammatory drugs for the treatment of IBD.
The intestine-specific Wnt-mimetic (SWAP), SZN-1326, is a bi-specific full-length human antibody that directly modulates Wnt signaling in target tissue by binding to particular Frizzled and LRP receptors that are highly expressed in intestinal crypts. It has the potential to stimulate intestinal stem cell proliferation, maturation and epithelial repair in IBD. In preclinical models of intestinal injury, SZN-1326 has demonstrated repair of damaged intestinal epithelium, improvements in disease activity, and anti-inflammatory effects.