BYON4228 + rituximab

BYON4228 + rituximab is a combination of two monoclonal antibodies under investigation for the treatment of relapsed/refractory CD20-positive B-cell non-Hodgkin’s lymphoma. BYON4228 is a humanized, pan-allelic antagonistic monoclonal antibody targeting signal regulatory protein alpha (SIRPα) on innate immune cells such as monocytes, macrophages, and neutrophils. It blocks the interaction between SIRPα and CD47—a pathway that transmits a "don't eat me" signal to immune cells—thereby enhancing macrophage and neutrophil-mediated destruction of tumor cells opsonized by therapeutic antibodies like rituximab. Unlike some other anti-SIRPα agents, BYON4228 does not bind SIRPγ on T cells, preserving T cell function. Rituximab is an anti-CD20 monoclonal antibody approved for various B-cell malignancies; it works by targeting CD20 on B lymphocytes leading to their depletion through multiple immune mechanisms including antibody-dependent cellular cytotoxicity (ADCC), complement activation, and direct apoptosis induction. The combination aims to synergistically enhance antitumor activity by both directly depleting malignant B-cells (rituximab) and overcoming tumor immune evasion via blockade of the CD47-SIRPα axis (BYON4228). Clinical development is ongoing in Phase 1 trials for lymphoma[1][2][3][5][6].

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