Sabatolimab (DB16322): A Comprehensive Report on a First-in-Class TIM-3 Immuno-Myeloid Therapy

Executive Summary

Sabatolimab, also known as MBG453, is an investigational, first-in-class, high-affinity, humanized Immunoglobulin G4 (IgG4​) monoclonal antibody engineered to target the T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3).[1] The scientific rationale for its development was based on a compelling dual-mechanism hypothesis. First, as an immune checkpoint inhibitor, Sabatolimab was designed to block the inhibitory TIM-3 pathway, thereby reactivating exhausted T-cells and other components of the innate and adaptive immune systems to mount an anti-tumor response.[2] Second, and of particular importance in hematologic cancers, Sabatolimab was intended to directly target TIM-3 expressed on the surface of leukemic stem cells (LSCs) in myeloid malignancies such as Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML), potentially disrupting LSC self-renewal and facilitating their elimination.[4]

This dual immuno-myeloid mechanism of action prompted the initiation of the ambitious STIMULUS clinical trial program by Novartis. This program was designed to comprehensively evaluate the safety and efficacy of Sabatolimab, primarily in combination with hypomethylating agents (HMAs), across a spectrum of myeloid disorders.[6] Early-phase studies yielded promising results, showing high objective response rates and durable responses, which supported the drug's advancement into late-stage development and led to the granting of Fast Track and Orphan Drug designations by US and EU regulators, respectively.[7]