ACT-903 links ACT-101 to a proprietary maytansine payload with a glutathione-sensitive linker (drug-antibody ratio ~5.96). It targets AFP receptors on cancer cells and MDSCs. AFP receptors are absent on normal adult cells in studies to date. The receptor has not yet been clinically validated; that is what the planned clinical studies are for.

Preclinical data: In an ovarian cancer xenograft study (A2780, Southern Research), ACT-903 eliminated tumors completely in all treated animals, with no regrowth to day 62, while all control animals had died by day 34. That study used immunodeficient mice, so the immune effect of removing MDSCs remains to be demonstrated in clinical studies. ACT-903 has not yet been tested in humans, and its safety will be established in Phase I.

Clinical plan: A Phase Ia/b multiple-ascending-dose basket study is planned, enriched to an orphan cancer indication such as platinum-resistant ovarian cancer or testicular germ cell cancer, at Princess Margaret Cancer Centre and one US centre. The study has not yet begun; IND-enabling work is ongoing.

Intellectual property: European patent claims covering ACT’s three-component combination (ACT-101 + linker + maytansine) have been granted, with coverage to 2042 and beyond. Applications in the US, China, India, and Canada are pending.

Manufacturing: Absci has developed the E. coli cell line that produces ACT-101. The line transfers to a contract manufacturer for cGMP production, and Abzena performs the conjugation step.