Validation of a novel anti-BMP2/4 inhibitor for treatment of Barrett’s esophagus

During the past decades the highly malignant Esophageal adenocarcinoma (EAC) has become an important health burden. Despite intensive treatments including chemo-and radiotherapy, and surgery, 5-year survival is less than 15%. The only way to improve survival is through more effective prevention. Barrett’s esophagus (BE) is a frequently occurring premalignant lesion of the esophagus that predisposes for EAC. At present, effective pharmacological eradication therapies for BE do not exist. Currently patients with BE are under periodic endoscopic surveillance to examine for early malignant changes in order to apply ablative therapies or surgery. These procedures are stressful, invasive and not cost effective.

This project has studied the molecular mechanisms underlying the development of BE and were able to develop highly specific antibodies, which target a specific signaling pathway involved in the development of BE. In preclinical in vivo studies it is demonstrated that these molecules effectively can inhibit the growth of Barrett cells and sustain development of the normal esophageal cells.

In this project the partnership of the AMC team with the company QvQ will join forces to demonstrate the safety of the molecules and provide more evidence that the cells that develop upon treatment of Barret mucosa are healthy and do not carry mutations. Also, the molecules will be humanised in order to prevent severe adverse events in humans. The outcomes will be a early safety profile and several humanised forms of the antibodies that will be ready for further GMP production and toxicity screening.