Drug intelligence / Profile preview

lintuzumab-Ac225 + venetoclax

Development stage: Unknown
Lead developer: Actinium Pharmaceuticals
Modality: Small Molecules, Antibody-Radionuclide Conjugates → Antibody Conjugates → Antibody-Based Therapeutics, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration: Intravenous, Oral

Overview

Lintuzumab-Ac225 + venetoclax is a **combination therapy** under clinical investigation for **relapsed/refractory acute myeloid leukemia (AML)**. Lintuzumab-Ac225 is a radioimmunoconjugate comprising a humanized monoclonal antibody (lintuzumab) targeting CD33, conjugated to the alpha-emitter radioisotope actinium-225. It delivers highly cytotoxic alpha radiation selectively to CD33-expressing AML cells, inducing DNA double-strand breaks. Venetoclax is a small molecule inhibitor of BCL2, a key anti-apoptotic protein. This combination is designed to overcome venetoclax resistance by using DNA damage from lintuzumab-Ac225 to reduce MCL1 levels, promoting apoptosis in AML cells and increasing tumor sensitivity to venetoclax. Preclinical and early clinical data indicate strong synergy in killing venetoclax-resistant AML cells and improving survival in animal models. The combination is being tested in phase I/II trials in patients with relapsed/refractory AML[1][3][7].

Brand names: Actimab-AVenclexta
Other names: Actinium-225 (225Ac)-lintuzumab + venetoclax225Ac-lintuzumab + venetoclaxlintuzumab Ac-225 + venetoclax

Targets

BCL-2 (BCL-2 family)CD33 (Myeloid cell surface antigen CD33)

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