ABL602 / ABL Bio - LARVOL DELTA

Bispecific antibody (ABL602 2 + 1) induced bistable acute myeloid leukemia kinetics. (PubMed, Sci Rep) - "Our finding explains observed phenomenon that bispecific antibody was less efficacious at high tumour burden even with enough activated cytotoxic CD8 + T cells. Maintaining high antibody concentration and preventing T-cell exhaustion are equivalently important to sustain long-term control."

Journal • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD8

Asymmetric anti-CLL-1×CD3 bispecific antibody, ABL602 2+1, with attenuated CD3 affinity endows potent antitumor activity but limited cytokine release. (PubMed, J Immunother Cancer) - "With its potent tumor-killing activity and reduced cytokine release, ABL602 2+1 is a promising candidate for treating patients with AML and warrants further study."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • IL6 • TNFA

Asymmetric anti-CLL-1×CD3 bispecific antibody, ABL602 2+1, with attenuated CD3 affinity endows potent antitumor activity but limited cytokine release (J Immunother Cancer) - "ABL602 2+1 showed a limited CD3 binding in the absence of CLL-1, suggesting that steric hindrance on the CD3 binding arm could reduce CLL-1 expression-independent CD3 binding. Although the CD3 binding activity was attenuated compared with that of 1+1, ABL602 2+1 exhibited much stronger T-cell activation and potent tumor-killing activities in AML cell lines. ABL602 2+1 efficiently inhibited tumor progression in subcutaneously and orthotopically engrafted AML mouse models."

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

An asymmetrical CLL1/CD3 bispecific antibody, ABL602, exhibits CLL1 binding-dependent CD3 binding/activation and antitumor activity in acute myeloid leukemia (AML) mouse model and leukemia blasts from AML patients (ESMO 2022) - "ABL602 induced superior tumor cell killing than 1+1 reference antibody JNJ-67571244. In AML patient blasts, CLL1 was highly expressed and ABL602 exhibited a strong T cell activation and tumor killing activity on CLL1 + AML blasts. Conclusions This study supports the target-specific T cell activation and tumor killing activity of 2+1 heterodimeric structure of ABL602 on both AML cell lines and patient-originated AML blasts and warrants further pre-clinical development."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • CD33

ABL Bio's AML treatment to draw attention at ESMO 2022 (Korea Biomedical Review) - "ABL Bio said it would disclose pre-clinical data of ABL602, an acute myeloid leukemia (AML) treatment, at the European Society for Medical Oncology (ESMO 2022) meeting in early September....The upcoming data release follows the company's presentation of ABL602's animal model results at the American Society of Hematology meeting in the US in December (ASH 2021)....'ABL602 induced potent cytotoxic activities on CLL1-expressing AML cell lines with concomitant T cell activation and cytokine/granzyme B release,' the research team said. 'Despite the strong antitumor activity, ABL602 preserved CLL-1-negative cancer cell lines. This indicates that ABL602 induces CLL-1-dependent cytotoxicity'....This time, the company will add data from AML patients' leukemia blasts."

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

A Novel Asymmetrical Anti-CLL-1×CD3 Bispecific Antibody, ABL602, Induces Potent CLL1-Specific Antitumor Activity with Minimized Sensitization of Pro-Inflammatory Cytokines (ASH 2021) - "ABL602 exhibited higher binding activity to CLL-1-expressing AML cell lines and greater tumor-killing efficacy than 1+1 format BsAb and benchmark antibody MCLA-117 (Merus; CLEC12AxCD3 bispecific antibody). Proportions of bone marrow CD33 + AML blasts diminished in a dose-dependent manner, while CD3 + T cells more infiltrated to the bone marrow. Overall, our results indicate that ABL602, appropriately engineered 2+1 asymmetric BsAb, promotes T-cell activity specifically against CLL1-expressing AML cells and is a promising treatment strategy for AML patients by achieving the desired balance between antitumor activity and safety."

Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • GZMB • IL6 • TNFA