NC525 / NextCure - LARVOL DELTA

A LAIR-1 targeting antibody drug conjugate for hematologic cancers. (ASCO 2025) - "LAIR-1 ADCs appear safe in human LAIR-1 KI mice. LAIR-1 ADC was highly effective in eradicating and controlling both leukemia and lymphoma tumors that expressed LAIR-1. Together, this study supports the development of a LAIR-1 ADC for the treatment of LAIR-1 expressing hematological cancers."

Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • LAIR1

A Safety, Tolerability and Efficacy Study of NC525 in Subjects With Advanced Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=28 | Terminated | Sponsor: NextCure, Inc. | N=63 ➔ 28 | Trial completion date: May 2025 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2025 ➔ Jan 2025; As a result of program reprioritization and due to the limited clinical activity observed in the Phase 1 trial, the study has been discontinued.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Safety, Tolerability and Efficacy Study of NC525 in Subjects with Advanced Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=63 | Active, not recruiting | Sponsor: NextCure, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

LAIR-1 agonism as a therapy for acute myeloid leukemia. (PubMed, J Clin Invest) - "We showed that LAIR-1 agonism drives a unique apoptotic signaling program in leukemic cells that was enhanced in the presence of collagen. NC525 also significantly improved the activity of azacitidine and venetoclax to establish LAIR-1 targeting as a therapeutic strategy for AML that may synergize with standard-of-care therapies."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • LAIR1

NextCure Publishes Non-Clinical Data Defining the Mechanism of Action for NC525, a Novel LAIR-1 Antibody for AML (GlobeNewswire) - "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....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."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

NextCure Provides Business Update and Reports Third Quarter 2023 Financial Results (GlobeNewswire) - "Q3 2023 Business Highlights and Updates: (i) Phase 1b updates for NC410 (LAIR-2 Fusion) and NC762 (B7-H4 mAb) by year end; (ii) Operational update for NC525 (LAIR-1 mAb) Phase 1a by year end."

P1 data • Trial status • Hematological Malignancies • Solid Tumor

NextCure Provides Business Update and Reports Second Quarter 2023 Financial Results (GlobeNewswire) - "NC525 (LAIR-1 mAb): Continued enrollment in the Phase 1 monotherapy dose escalation and safety study evaluating NC525 in AML patients; Phase 1a update is expected in the fourth quarter of 2023."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

NextCure Presents Non-Clinical Data Defining the Mechanism of NC525 at the 2023 Federation of Clinical Immunology Societies (FOCIS) Annual Meeting (GlobeNewswire) - "NextCure...announced the presentation of a poster that defines the mechanism of NC525-induced apoptosis of leukemic cells, but not healthy hematopoietic cells, at the Federation of Clinical Immunology Societies (FOCIS) annual meeting in Boston....'The data presented in the poster define the mechanism that leads to specific induction of apoptosis in leukemic cells, but not in healthy immune cells. We look forward to continuing NC525’s clinical development and providing an update on the trial in the fourth quarter of this year.”'"

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

NextCure Provides Business Update and Reports First Quarter 2023 Financial Results (GlobeNewswire) - "NextCure, Inc...today provided a business update and reported first quarter 2023 financial results. NC410 (LAIR-2 fusion): Continued enrollment in the Phase 1b/2 clinical trial evaluating NC410 in combination with pembrolizumab in patients with immune checkpoint refractory or naïve solid tumors. Phase 1b update is expected in the fourth quarter of 2023. NC762 (B7-H4 mAb): Continued enrollment in the Phase 1b dose expansion study in patients with solid tumors and high expression of B7-H4. Phase 1b update is expected in the fourth quarter of 2023. NC525 (LAIR-1 mAb)...Initial Phase 1a data are expected in the fourth quarter of 2023."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

A Safety, Tolerability and Efficacy Study of NC525 in Subjects With Advanced Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=63 | Recruiting | Sponsor: NextCure, Inc.

Metastases • New P1 trial • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

NextCure Provides Business Update and Reports Full Year 2022 Financial Results (GlobeNewswire) - "Business Highlights and Near-Term Milestones - NC525 (LAIR-1 mAb): (i) Dosed the first patient in a Phase 1 monotherapy dose escalation and safety study evaluating NC525 in AML patients in February 2023; (ii) Initial Phase 1a data is expected in the fourth quarter of 2023."

P1 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Phase 1, Open-Label, Safety, Tolerability, and Efficacy Study of NC525 in Subjects with Advanced Myeloid Neoplasms (ASH 2022) - "Safety and tolerability will be further assessed through the expansion of a few dose levels to determine an optimal recommended Phase 2 Dose (RP2D) and administration schedule of NC525, based on the PK/PD profiles. Taken together, preclinical data suggest that targeting LAIR-1 in AML and other myeloid malignancies may be an effective therapy for these diseases with the advantage of specifically eradicating leukemic stem cells and sparing normal HSCs."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • BCL2 • CD34 • LAIR1

NextCure to Present Trial in Progress Poster for NC525 at the 2022 American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "NextCure...announced that clinical trial investigator Nicholas Short, M.D., Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, Texas, will present a Trials in Progress poster for NC525, a novel first-in-class immunomedicine, at the American Society of Hematology (ASH) annual meeting....'We have recently filed our investigational new drug (IND) application with the US Food and Drug Administration (FDA) and have received the green light to proceed with a Phase 1 clinical study. We look forward to initiating it in Q1 2023 and advancing NC525 as a potential therapeutic option'."

Clinical protocol • IND • New P1 trial • Hematological Malignancies • Oncology

NextCure Provides Business Update and Reports Fourth Quarter and Full Year 2021 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: (i) NC318 Phase 2 update: fourth quarter of 2022 (Amended Phase 2: S15+ selection with CLIA assay, 800 mg dosed Q1W); (ii) NC318 anti-PD-1 Combo (Yale University Investigator-Initiated trial): second half of 2022; (iii) NC410 Phase 1 update: second half of 2022; (iv) NC762 initial Phase 1 data: second half of 2022; (v) NC525 Investigational New Drug Application (IND) filing: fourth quarter of 2022."

IND • P1 data • P2 data • Acute Myelogenous Leukemia • Breast Cancer • Head and Neck Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Novel Lair-1 Antibody Selectively Targets Acute Myeloid Leukemia (AML) Stem Cells (ASH 2021) - "Extensive research has led to recent approval of novel therapies such as mylotarg, venetoclax, glasdegib and CC486, and small molecule inhibitors against actionable mutations such as ivosidenib (IDH1), enasidenib (IDH2), gliteritinib and midostaurin (FLT3) in AML...Taken together, our studies suggest that the LAIR-1 mAb we generated is a novel AML immunomedicine that preferentially eradicates AML LSCs and blasts while preserving healthy HSCs through disruption of AML survival signals and clearance of AML through ADCP and ADCC. Additional studies are currently evaluating if this novel LAIR-1 mAb has other mechanisms of action that contribute to overall in vivo activity, including reduction of AML niche implantation, regulation of bone marrow homing and regulation of anti-tumor immunity."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Oncology • Transplantation • CD19 • CD22 • CD33 • CD34 • CD99 • FLT3 • IDH1 • IDH2 • KIT • LAIR1 • THY1

NextCure and Collaborators Provide Data on Targets in Development at American Society of Hematology Annual Meeting (GlobeNewswire) - "The LAIR-1 mAb was shown to preferentially target and kill LAIR-1 expressing AML LSCs and blast cells....The mAb exerts its anti-tumor activity via disruption of survival signals in leukemic cells and Fc-mediated effector functions."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology