NextCure Publishes Non-Clinical Data Defining the Mechanism of Action for NC525, a Novel LAIR-1 Antibody for AML
BELTSVILLE, Md., Nov. 15, 2023 (GLOBE NEWSWIRE) -- NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases, today announced the publication of a manuscript titled “LAIR-1 Agonism as a Therapy for Acute Myeloid Leukemia” in the Journal of Clinical Investigation. The data demonstrate that NC525 induces cell death in acute myeloid leukemia (AML) blast cells and leukemic stem cells (LSCs) through leukocyte-associated immunoglobin-like receptor-1 (LAIR-1) agonism by driving a unique apoptotic signaling pathway.
NC525 is a humanized monoclonal antibody (mAb) that specifically binds to LAIR-1 and kills LSCs, while sparing healthy hematopoietic stem cells (HSCs). The publication details a novel mechanism for the potential treatment of AML, as the expression level of the LAIR-1 receptor on leukemic cells acts as a key regulator. High expression of LAIR-1 is commonly seen on LSCs and blast cells and plays a role in survival of these cancer cells. In contrast, LAIR-1 expression is relatively lower on healthy HSCs and does not play a role in survival of normal immune cells. This makes LAIR-1 a promising anti-leukemic target.
“Current standard-of-care (SoC) treatments eliminate leukemic blast cells, and both leukemic stem cells and healthy hematopoietic stem cells, resulting in neutropenia and thromboytopenia and sub-optimal therapies. In addition, eventual failure of SoC is primarily through the emergence of chemotherapy resistant LSCs,” said Solomon Langermann, Ph.D., NextCure’s chief scientific officer. “We have shown in patient-derived xenograft models that NC525 can specifically eliminate both leukemic stem cells and AML blast cells, including leukemic cells resistant to SoC, while sparing healthy progenitor cells, demonstrating NC525’s potential as a novel treatment for AML.”
In addition to its potential therapeutic effects as a monotherapy, the publication highlights that NC525 synergizes with, and improves the activity of, ventoclax and azacytidine (VEN-AZ), the current SoC therapy in AML. The combination kills leukemic cells from patients refractory to VEN-AZ. Thus, NC525 holds great promise as an important and novel treatment for patients with resistant and refractory AML (R/R AML).
A Phase 1 study with NC525 is underway as an open-label, non-randomized, dose escalation trial to determine safety and tolerability of NC525 in adult patients with relapsed or refractory AML.
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