FDA grants orphan drug designation to ISB 2001

On July 7, 2023, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to ISB 2001, a first-in-class trispecific antibody, for the treatment of relapsed/refractory multiple myeloma.¹ At the 2023 American Association for Cancer Research (AACR) Annual Meeting, Perro² shared the initial preclinical data on the feasibility of ISB 2001 in relapsed/refractory multiple myeloma. The Multiple Myeloma Hub summarizes this presentation here.

ISB 2001²

ISB 2001 is a T cell-engaging trispecific antibody, featuring three antigen-binding arms to simultaneously bind CD3 on T cells and BCMA/CD38 on myeloma cells (Figure 1). Targeting both BCMA and CD38 increases avidity-based binding, increasing specificity to myeloma cells and subsequently cell death.

Figure 1. Mechanism of action of ISB 2001* 

*Adapted from Perro.² Created with BioRender.com.

Key points²

• In vivo, ISB 2001 resulted in a complete remission rate of 100% in a mouse model.
• The half-life in a human FcRn transgenic mouse model was 7.6 days.
• Ex vivo, ISB 2001 demonstrated increased rates of cytotoxicity compared with other BCMA-targeted T cell engagers: alnuctamab, teclistamab, and EM-801.
• Ex vivo, ISB 2001 demonstrated higher potency in smoldering, newly diagnosed, and RRMM than teclistamab.