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

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

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 Disorders • Hematological Malignancies • Leukemia • Oncology • CD27 • CD70

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

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. | Not yet recruiting ➔ Recruiting

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

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. | Phase classification: P1b ➔ P1 | Trial completion date: May 2024 ➔ May 2025 | Trial primary completion date: May 2024 ➔ May 2025

Combination therapy • Phase classification • 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 2023 ➔ Aug 2024

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

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 | Not yet recruiting | Sponsor: OncoVerity, Inc.

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

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 • CD27 • CD70 • MKI67

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 • Transplantation • CD27 • CD34 • CD70 • LTBR • TNFA

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas. (PubMed, Cells) - "Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs."

IO biomarker • Journal • Review • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • CCR4 • CD123 • CD70 • IL3RA

Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study. (PubMed, Lancet Haematol) - P1b, P2 | "Although part one of this study was not designed to formally compare the two dose cohorts for efficacy, the totality of clinical data for cusatuzumab studies performed to date indicate that cusatuzumab 20 mg/kg plus azacitidine represents the optimal dose for further studies. A phase 1b study investigating the triple combination of cusatuzumab with venetoclax and azacitidine is underway (NCT04150887)."

Clinical • Journal • P1 data • P2 data • P2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • CD70

The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via Fc-mediated effector functions, and interrupts CD70/CD27 signaling. (PubMed, Front Oncol) - "In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively...A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models...IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling."

IO biomarker • Journal • Burkitt Lymphoma • Head and Neck Cancer • Hematological Malignancies • Kidney Cancer • Lung Cancer • Lymphoma • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD27 • CD70 • SIRPA

METTL3 inhibition induced by M2 macrophage-derived extracellular vesicles drives anti-PD-1 therapy resistance via M6A-CD70-mediated immune suppression in thyroid cancer. (PubMed, Cell Death Differ) - "Furthermore, blocking CD70 using cusatuzumab, a high-affinity monoclonal antibody, reversed the anti-PD-1 therapy resistance induced by M2 EVs in vivo. Finally, we demonstrated that METTL3 expression negatively correlated with CD70 expression and M2 macrophages and Tregs infiltration in PTC and ATC tissues. Our findings provide new insights into developing novel therapies for advanced PTC and ATC."

IO biomarker • Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • CD70 • METTL3 • MIR21 • YTHDF2

CD70/CD27 SIGNALING PROMOTES THE EXPANSION OF CLONAL PLASMA CELL SUBSETS IN MULTIPLE MYELOMA (EHA 2023) - "In this regard, different Abs and Ab-derivates were tested including a CD70 blocking antibody (αCD70) and an antibody-dependent cell-mediated cytotoxicity (ADCC) optimized antibody (cusatuzumab) that activates FcγR-expressing effector cells... Although the treatment options of MM have rapidly increased during the last years, MM remains an incurable disease that ultimately leads to death. Our results indicate that especially advanced MM stages express high levels of CD70. In addition, our results indicate that CD70/CD27 cell-autonomous signaling contributes to disease progression and therapy resistance and identifies CD70 as potential target in MM."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Immune Modulation • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • CD27 • CD70 • MKI67

VHH-based chimeric antigen receptor T cells against CD70 to eliminate primary and re-challenge renal cell carcinoma tumors in preclinical study. (ASCO 2023) - "These CAR constructs include 4 VHH sequences and a human scFv containing VH and VL derived from cusatuzumab... Our results indicate a promising VHH-based CD70 CAR-T cells for RCC therapy, supporting further development for future clinical trial and application."

CAR T-Cell Therapy • Preclinical • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD70 • IL2

Preclinical development of a monoclonal antibody targeting CD70 as cancer immunotherapy (AACR 2023) - "Notably, in a U266 multiple myeloma model, IMM40H, at the dose of 0.3 mg/kg, completely inhibited tumor growth in a way that therapeutic effects appeared significantly earlier than that of cusatuzumab at a higher dose of 1 mg/kg. Therapeutic effects of IMM40H at the dose of 3 mg/kg also appeared earlier than that of bortezomib at the dose of 0.5 mg/kg. Interestingly, combination of IMM40H and IMM01 (a SIRPα-IgG1 Fc fusion protein targeting CD47) generated significant therapeutic synergy in models of A498 kidney cancer and Raji lymphoma...IND of IMM40H has been approved in China and US. This antibody is now in a phase 1 study in patients with advanced malignancies expressing CD70."

IO biomarker • Preclinical • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Malignancies • Kidney Cancer • Lung Cancer • Lymphoma • Mesothelioma • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • CD47 • CD70 • SIRPA

OncoVerity, Inc. Announces Exclusive Worldwide Licensing Rights to Cusatuzumab and Appoints Max Colao as Chief Executive Officer (Businesswire) - "OncoVerity...has secured worldwide licensing rights to cusatuzumab from argenx and received $30M in funding from argenx and a joint venture of UCHealth and University License Equity Holdings, Inc. on the University of Colorado Anschutz Medical Campus for its continued development. Cusatuzumab is a first-in-class anti-CD70 antibody that has generated promising results in early acute myeloid leukemia (AML) human studies. OncoVerity will optimize cusatuzumab’s continued development in AML and explore its application in other cancers."

Licensing / partnership • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Management of AML in the elderly (PubMed, Bull Cancer) - "In recent years, many molecules have shown very interesting efficacy, often targeted therapies whose indication is based on a specific mutation profile (gilteritinib, ivosidenib), or mutation-independent (venetoclax), but also drugs whose indication is based on a specific biomarker (tamibarotene) or on new generation immunotherapies targeting macrophages (magrolimab) or other immune effectors while targeting leukemic cells resulting in forced immunological synapse (flotetuzumab) or activation of lymphocyte effectors associated with inhibition of the AML cells' stem signature in their microenvironment (cusatuzumab sabatolimab). All of these new strategies are discussed in this review, as well as the challenges of this frail population, which has benefited in recent months from all the major advances in the field, questioning in a second phase the modification of practices in younger patients."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology

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

ELEVATE: Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia (clinicaltrials.gov) - P1b | N=61 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jun 2023 ➔ May 2024 | Trial primary completion date: Dec 2022 ➔ May 2024

Combination therapy • 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: Janssen Research & Development, LLC | Trial primary completion date: Dec 2022 ➔ Aug 2023

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

A Study of ARGX-110 in Combination With Azacytidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) or High Risk Myelodysplatic Syndrome (MDS) (clinicaltrials.gov) - P1/2 | N=38 | Completed | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD27

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: Janssen Research & Development, LLC | Trial completion date: Dec 2022 ➔ Aug 2023

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

Cusatuzumab Plus Azacitidine in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia Ineligible for Intensive Treatment. (PubMed, Cancer Sci) - "No dose limiting toxicity was observed during the study period. The combination of cusatuzumab and azacitidine is generally well tolerated in Japanese participants and further exploration of this combination is warranted."

Journal • Acute Myelogenous Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Oncology • CD70