On April 17, 2023 Byondis B.V., an independent, clinical-stage Dutch biopharmaceutical company creating precision medicines, reported that the Journal for ImmunoTherapy of Cancer (the official journal of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)) has published encouraging preclinical data on its investigational monoclonal antibody (mAb) BYON4228 (Press release, Byondis, APR 17, 2023, View Source [SID1234630196]).
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BYON4228 targets and blocks the Cluster of Differentiation 47-Signal Regulatory Protein alpha (CD47-SIRPα) interaction responsible for tumors’ ability to escape recognition and destruction by the immune system. The Byondis paper, "BYON4228 is a pan-allelic antagonistic SIRPα antibody that potentiates destruction of antibody-opsonized tumor cells and lacks binding to SIRPγ on T cells," reports the findings of an extensive preclinical characterization of the novel SIRPα-directed antibody, including direct comparisons to previously reported anti-SIRPα antibodies. Side-by-side comparisons show that BYON4228 has a unique and favorable preclinical profile. The therapy is scheduled to enter First-in-Human (Phase I) study later this year. The Phase I clinical study (NCT05737628) is designed to evaluate BYON4228 alone and in combination with rituximab in patients with relapsed/refractory CD20-positive B-cell non-Hodgkin’s lymphoma.
Byondis Chief Scientific Officer Wim Dokter, Ph.D. explains: "BYON4228 is a pan-allelic antibody, meaning it recognizes the two major SIRPα variants in humans. In addition, because BYON4228 does not recognize SIRPγ, a related molecule on T cells, it should not compromise T cell activity."
"This implies that the therapy could benefit all eligible patients. Used in combination, BYON4228 can potentially increase the efficacy of a wide range of therapeutic mAbs in different blood and solid cancers," Byondis Chief Executive Officer Marco Timmers, Ph.D. added.
According to the published data, BYON4228 potentiates macrophage- and neutrophil-mediated killing of both hematologic and solid cancer cells in vitro in the presence of a variety of tumor-targeting antibodies, including trastuzumab, rituximab, daratumumab, panitumumab and cetuximab. In vivo, BYON4228 promotes the anti-tumor activity of such antibodies. Finally, BYON4228 shows a favorable preclinical safety profile.
More About BYON4228
BYON4228 is a humanized therapeutic monoclonal antibody designed to stimulate the innate immune system. It binds to SIRPα expressed on innate immune cells, especially monocytes, macrophages and neutrophils. BYON4228 blocks binding of SIRPα to CD47 (a cell surface molecule often over-expressed on cancer cells), preventing signaling through the CD47-SIRPα axis. The CD47-SIRPα axis limits the antibody-mediated destruction of cancer cells by transducing a "don’t eat me" signal to the immune system. By inhibiting the CD47-SIRPα axis, BYON4228 prevents the inhibitory "don’t eat me" signal to be detected, thereby stimulating the immune cell to do what it is supposed to do: destroy the tumor cell.
As a pan-allelic antagonistic SIRPα antibody that lacks binding to SIRPγ on T cells, BYON4228 has the potential to become best in class. It distinguishes itself from previously reported SIRPα antibodies that in all probability are representative of antibodies currently being tested in clinical trials.