cusatuzumab (ARGX-110) / argenx, OncoVerity - LARVOL DELTA

Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy. (PubMed, Haematologica) - "Thus, cusatuzumab/azacitidine appears generally well tolerated and shows preliminary efficacy in this setting. Investigation of cusatuzumab combined with current standard-of-care therapy, comprising venetoclax and azacitidine, is ongoing."

Journal • P1/2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • CD70

Cusatuzumab combined with venetoclax with or without azacitidine in unfit patients with newly diagnosed acute myeloid leukemia: phase Ib ELEVATE study. (PubMed, Haematologica) - P1 | "Sixteen patients were treated with CV and had similar safety but less favorable responses and survival than those treated with CVA. These results support further development of CVA for the treatment of AML (clinicaltrials.gov identifier: NCT04150887)."

Journal • P1 data • Acute Myelogenous Leukemia • Constipation • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • CD34 • CD70

Humanized CD70-targeted CAR-T cells with reduced fratricide demonstrate potent antitumor activity against AML and RCC. (PubMed, Int Immunopharmacol) - "Using an analog of the clinical-stage anti-CD70 antibody ARGX-110 as a reference, we screened a phage display library from immunized mice and identified high-affinity anti-CD70 antibodies, which were then used to construct a panel of second-generation CARs...In xenograft models, A174-hu1-CAR-T infusion demonstrated potent antitumor efficacy against both AML and RCC, with a favorable safety profile. Overall, we developed a humanized CD70-targeted CAR-T cell therapy, A174-hu1-CAR-T, with reduced fratricide and potent antitumor activity, providing a preclinical foundation to support further translational development."

IO biomarker • Journal • Acute Myelogenous Leukemia • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Oncology • Renal Cell Carcinoma • Solid Tumor • CD70

Engineering CD16-Enhanced Stem Cell–Derived Universal NKT Cells to Potentiate Anti-CD70 Therapy in Renal Cell Carcinoma (KCRS 2026) - "This combinatorial strategy represents a promising approach to overcoming current limitations of monoclonal antibody therapy and advancing next-generation immunotherapies for solid tumors. Keywords Renal cell carcinoma (RCC); CD70; cusatuzumab; natural killer T (NKT) cell; cell therapy"

Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD70

[89Zr]Zr-RDT-008: A Site-Specifically Radiolabeled Anti-CD70 Antibody for Immuno-PET Imaging of Clear Cell Renal Cell Carcinoma (SNMMI 2026) - "In CD70 overexpressing 786-O cells, [89Zr]Zr-RDT-008 showed 74.0 +/- 7.45% internalization rate, outperforming clinical stage antibodies (cusatuzumab: 20.6 +/- 1.73%, vorsetuzumab: 33.9 +/- 2.41%). [89Zr]Zr-RDT-008 is the first 89Zr-labeled full-length anti-CD70 antibody demonstrating high-contrast, target-specific immuno-PET imaging of ccRCC. The site-specific conjugation strategy provides a homogeneous product suitable for clinical translation. This tracer may serve as a companion diagnostic for CD70-targeted therapies and warrants further investigation in clinical studies."

IO biomarker • IO Companion diagnostic • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CD27 • CD70

ELEVATE: Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: OncoVerity, Inc. | Trial completion date: May 2026 ➔ May 2027 | Trial primary completion date: May 2026 ➔ May 2027

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

OV-AML-1231: A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy (clinicaltrials.gov) - P2 | N=140 | Active, not recruiting | Sponsor: OncoVerity, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD4

CULMINATE: A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: OncoVerity, Inc. | Completed ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

OV-AML-1231: A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: OncoVerity, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD4

Comprehensive surfaceome proteomics uncovers CD70 as a novel immunotherapeutic target in natural killer/T cell lymphoma (NKTL) (AACR 2026) - "Lastly, in-house generated ADC through conjugation of Cusatuzumab with MMAE via VC-PAB linker showed efficacious response in NKTL. As such, our work characterized plasma membrane landscape of NKTL and shed light on targets with potential to become novel treatments for this dreadful disease."

IO biomarker • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD48 • CD70 • ITGA4

QLS2309, a trifunctional NKp46/CD16a-NK cell engager targeting CD70 enhances efficacy against acute myeloid leukemia via mitigating the refraction to therapeutic antibody-dependent cytotoxicity (AACR 2026) - P1 | "In vivo studies demonstrated dose-dependent tumor growth inhibition with QLS2309, showing superior efficacy compared to cusatuzumab (an ADCC-enhanced monoclonal antibody). These data support QLS2309 as a promising novel therapy for AML. A Phase 1 dose-escalation study in CD70+ relapsed/refractory hematologic malignancies is currently ongoing (NCT07173595)."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD70 • FCGR3A • TNFA

OV-AML-1231: A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: OncoVerity, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD4

CD70/CD27 signaling promotes the pathogenesis of multiple myeloma and represents a promising therapeutic target. (PubMed, Leukemia) - "Furthermore, the ADCC-enhanced anti-CD70 antibody, cusatuzumab, demonstrated high efficacy in treating myeloma in xenotransplantation models. Collectively, these findings underscore the critical role of CD70/CD27 signaling in activating MAPK/ERK and Wnt pathways essential for MM progression. Targeting CD70 with blocking or ADCC-enhanced antibodies represents a promising therapeutic strategy, particularly for advanced MM stages characterized by high CD70 expression."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD27 • CD70

CD70/CD27 signaling promotes the pathogenesis of multiple myeloma and represents a promising therapeutic target (Nature) - "This proliferative advantage results in elevated CD70 expression in advanced MM stages, particularly in extramedullary myeloma. Functional inhibition of CD70/CD27 signaling, achieved either by generating CD70-knockout primary MM cells or with blocking monoclonal antibodies, completely abrogated tumor growth in xenotransplantation models. Furthermore, the ADCC-enhanced anti-CD70 antibody, cusatuzumab, demonstrated high efficacy in treating myeloma in xenotransplantation models."

Preclinical • Multiple Myeloma

CULMINATE: A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy (clinicaltrials.gov) - P2 | N=103 | Completed | Sponsor: OncoVerity, Inc. | Active, not recruiting ➔ Completed

Trial completion • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

IL-17–Induced CD70 expression promotes T-cell suppression in DLBCL: Implications for immune escape and T-cell exhaustion (ASH 2025) - "Collectively, our data demonstrate a previously unidentified IL-17/CD70 axis that plays acritical role in regulating immune escape in DLBCL cells. Based on our findings, we propose therepurposing of FDA orphan drug CD70 neutralizing antibody Cusatuzumab (ARGX-110) for DLBCLtreatment to reduce the risk of relapse and improve outcomes following R-CHOP therapy. Furthermore,this discovery may contribute to a better understanding of the potential outcomes and treatmentresponses of DLBCL patients to conventional chemotherapy regimens."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • CAFs • CD4 • CD70 • FOXP3 • HAVCR2 • IL10 • IL17A • IL2 • PD-1 • TNFA

Trial in Progress: A Multicenter, Open Label, Randomized, Phase 2 Study of Venetoclax and Azacitidine Plus Cusatuzumab Versus Venetoclax and Azacitidine Alone in Newly Diagnosed AML Patients Who Are Not Candidates for Intensive Therapy (ASH 2024) - P1, P1/2, P2 | "Patients with prior exposure to hypomethylating agents are excluded. This ongoing, multicenter, randomized study may inform new frontline low-intensity therapeutic options for newly diagnosed AML patients with high-risk biological features."

Clinical • IO biomarker • P2 data • Acute Myelogenous Leukemia • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Leukemia • Oncology • CD27 • CD70

Monoclonal Antibodies Targeting LIGHT Block Ltbr Signalling and Eliminate Acute Myeloid Leukemia Stem Cells (ASH 2023) - "We recently documented that targeting CD70, the ligand of the tumor necrosis factor receptor (TNFR) CD27, by the antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced monoclonal antibody (mAb) cusatuzumab eliminates LSC...Our findings reveal that LIGHT/LTbR-signalling is crucial for the pathogenesis of AML and especially for the maintenance and expansion of LSCs. We developed and validated novel LIGHT targeting mAbs in vitro and in vivo for further development in clinical trials."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD27 • CD34 • CD70 • LTBR • TNFA

CD70/CD27 Signaling Promotes Expansion of Clonal Plasma Cells in Multiple Myeloma and Is a Promising Therapeutic Target in Advanced Disease (ASH 2023) - "Moreover, different monoclonal antibodies (Abs) and Ab-derivates were tested including a CD70 blocking antibody (αCD70) and an antibody-dependent cell-mediated cytotoxicity (ADCC) optimized antibody (cusatuzumab, ArgenX) that activates FcγR-expressing effector cells to assess the therapeutic potential of targeting CD70 in MM... Our results indicate that CD70-expressing MM cells have a stem-cell like phenotype and propagate the disease. Targeting CD70 is a promising new therapy especially in advanced disease."

IO biomarker • Metastases • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma • CD27 • CD70 • MKI67

CULMINATE: A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: OncoVerity, Inc. | Trial completion date: Aug 2025 ➔ May 2026

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

SURFACEOME PROFILING FOR THE IDENTIFICATION OF NOVEL IMMUNOTHERAPEUTIC TARGETS IN NATURAL KILLER/T CELL LYMPHOMA (ICML 2025) - "As such, our work characterized plasma membrane landscape of NKTL and shed light on targets with potential to become novel treatments for this dreadful disease."

IO biomarker • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD48 • CD70 • ITGA4

CD70/CD27 SIGNALING PROMOTES CLONAL PLASMA CELL EXPANSION IN MULTIPLE MYELOMA AND REPRESENTS A PROMISING THERAPEUTIC TARGET (EHA 2025) - "Moreover, treatment with bortezomib, daratumumab or teclistamab upregulated CD70 expression in MM cell lines, leading to synergistic effects of cusatuzumab treatment with different drugs that are used as SOC in MM. CD70/CD27 signaling plays a crucial role in MM progression, particularly in advanced and refractory stages. Targeting CD70 with ADCC-enhanced antibodies, such as cusatuzumab, represents a promising therapeutic strategy for controlling MM growth and preventing relapse. Furthermore, combining CD70-targeting therapies with current MM treatments may offer enhanced therapeutic efficacy, positioning CD70 as a viable immunotherapeutic target in MM."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • CD27 • CD70

ELEVATE: Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: OncoVerity, Inc. | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: May 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

CULMINATE: A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: OncoVerity, Inc. | Trial completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

OncoVerity Secures Extended Series A to Advance Cusatuzumab in Newly Diagnosed AML (Businesswire) - "OncoVerity...announced today the closing of a Series A extension financing led by existing investors, argenx and RefinedScience....The proceeds from the Series A extension will fund the Phase 2 OV-AML-1231 trial of cusatuzumab, a novel, first-in-class high-affinity monoclonal anti-CD70 antibody, in combination with venetoclax and azacitidine for the treatment of newly diagnosed acute myeloid leukemia (AML)....Patient enrollment is underway, and the first eight patients have been dosed....'We are particularly excited about the potential of the Phase 2 trial, and look forward to sharing results from the interim analysis in the second half of 2025'."

Financing • P2 data • Trial status • Acute Myelogenous Leukemia