IGI's Trispecific Antibody for Multiple Myeloma Published in Nature Cancer

Ichnos Glenmark Innovation (IGI), a collaboration between Ichnos Sciences Inc. and Glenmark Pharmaceuticals Ltd., has announced significant preclinical findings for their trispecific antibody, ISB 2001. These findings, published in Nature Cancer, highlight ISB 2001's potential to address the issue of therapeutic resistance in multiple myeloma (MM).

Multiple myeloma is a challenging cancer to treat due to frequent relapses and resistance to existing therapies. Despite advances in monoclonal antibodies and bispecific therapies, overcoming these hurdles remains a critical need. ISB 2001, currently in Phase 1 clinical trials for relapsed or refractory multiple myeloma (r/r MM), represents a promising new approach by targeting multiple mechanisms of the disease.

The preclinical data show that ISB 2001 can effectively target and kill myeloma cells by binding to BCMA and CD38 on the tumor cells and CD3 on T cells. This trispecific interaction allows ISB 2001 to overcome resistance mechanisms that typically allow myeloma cells to evade treatment. The antibody's architecture is designed to maximize tumor cell killing while minimizing off-target effects on healthy cells.

Key findings from the study indicate that ISB 2001 is effective in killing tumor cells that have low expressions of BCMA or CD38, which are common resistance mechanisms. The in vitro, in vivo, and ex vivo studies demonstrated that ISB 2001 induces complete tumor regression in humanized mouse models and shows superior potency compared to other approved bispecific therapies and combination treatments.

Dr. Cyril Konto, President, Executive Director, and CEO of IGI, emphasized the significance of these findings, noting that they support the unique mechanism of action of IGI's multispecific antibody. The comprehensive preclinical data showcase the therapeutic potential of ISB 2001, which is currently being tested in clinical trials.

Dr. Mario Perro, Head of Biologics Research at IGI, highlighted the use of the proprietary BEAT® platform in developing ISB 2001. This platform enhances the antibody's specificity to MM cells while reducing unintended effects on non-target cells. The trispecific nature of ISB 2001 aims to boost immune cell activation and achieve more precise targeting and killing of tumor cells.

ISB 2001 stands out due to its trispecific design, which incorporates three antigen-binding arms. One arm targets the CD3 epsilon chain on T cells, while the other two bind to BCMA and CD38 on MM cells. Additionally, the antibody's Fc domain is modified to eliminate effector functions, ensuring that its activity is focused on redirecting T cells to attack tumor cells expressing BCMA and CD38. This dual targeting mechanism allows ISB 2001 to bind effectively to myeloma cells with very low antigen levels, thereby overcoming common resistance strategies.

Ichnos Glenmark Innovation (IGI) is a strategic partnership aiming to accelerate new cancer treatments. By combining Ichnos' expertise in novel biologics with Glenmark's experience in small molecule development, the collaboration seeks to advance innovative therapies for hematological malignancies and solid tumors. With a team of over 150 scientists and a robust pipeline of novel molecules, IGI leverages its three global innovation centers in the USA, Switzerland, and India to drive forward its mission.

These preclinical findings underscore the potential of ISB 2001 to become a significant advancement in the treatment of multiple myeloma, offering hope for more effective and durable responses in patients battling this challenging disease.

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