MAN-03

MAN-03 is an investigational, conditionally active bispecific T-cell engager (TCE) developed by Manifold Bio for the treatment of HER2-positive solid tumors. Engineered using the company's proprietary M-Design platform, MAN-03 is designed to remain relatively inactive in systemic circulation and become fully potent only upon reaching the tumor microenvironment (TME). This conditional activation is achieved through protein engineering that 'masks' the CD3-binding domain, which is then selectively 'unmasked' or activated by tumor-specific factors, such as proteases. By localizing T-cell recruitment and activation to the tumor site, MAN-03 aims to overcome the systemic toxicity and narrow therapeutic index common to traditional T-cell engagers, potentially enabling the treatment of cancers with varying levels of HER2 expression while reducing the risk of cytokine release syndrome (CRS) and on-target, off-tumor toxicity.