Targeting LAIR-1 with NC525: A Promising Approach for Advanced Myeloid Neoplasms Treatment

Acute Myeloid Leukemia (AML) is a condition that is largely untreatable for many patients using current treatment options. The persistence of leukemia-initiating cells, known as leukemic stem cells (LSCs), contributes to the high relapse rate, as these cells are resistant to standard chemotherapy. There is a significant need for new treatments that can target LSCs and reduce the risk of relapse, without harming healthy hematopoietic stem cells (HSCs).

Leukocyte Associated Immunoglobulin-like Receptor 1 (LAIR-1) is a receptor found on various immune cells and plays a role in creating an environment that suppresses the immune system. In the context of AML, LAIR-1's presence on AML blasts and LSCs is associated with a reduction in survival signals, which can lead to a decrease in the proliferation of these cells. Importantly, LAIR-1 is highly expressed on LSCs but barely detectable on normal HSCs, making it a promising target for anti-leukemia therapy.

NC525 is a monoclonal antibody designed to target LAIR-1 and has demonstrated several beneficial effects in preclinical studies. It has shown the ability to inhibit the growth of AML cells, spare the formation and differentiation of healthy HSCs, and directly kill AML cells without harming healthy leukocytes. It has also shown efficacy in various models, including reducing tumor growth in mice and inhibiting leukemia propagation in secondary transplant models.

A Phase 1 clinical trial is underway to evaluate the safety and tolerability of NC525 in adults with advanced myeloid neoplasms, including relapsed or refractory AML, MDS, or CMML. The trial will assess the pharmacologically active dose and the maximum tolerated dose of NC525, with the aim of determining an optimal recommended Phase 2 Dose and administration schedule.

The preclinical findings indicate that targeting LAIR-1 could be a promising therapeutic approach for AML and related disorders, with the potential to specifically eliminate LSCs while preserving normal HSCs.