Biond Biologics Begins Dosing BND-35 in Phase 1 Trial

Biond Biologics Ltd., a clinical-stage biopharmaceutical company headquartered in Misgav, Israel, has announced the commencement of a first-in-human clinical trial for BND-35. BND-35 is a humanized ILT3/LILRB4 antagonist antibody that has shown promise in preclinical studies for its potential to remodel the tumor microenvironment and improve immune response against cancer.

The initial patient has received the BND-35 monotherapy at the Institute of Oncology, Davidoff Center, Rabin Medical Center in Israel. This is one of six sites in Israel and the United States participating in the phase 1, open-label, dose-escalation study. The objective of the study is to evaluate the safety, tolerability, anti-tumor activity, pharmacokinetics, and exploratory biomarkers of BND-35 as a monotherapy and in combination with two approved drugs: a PD-1/PD-L1 inhibitor or the anti-EGFR drug, cetuximab.

The trial design includes unique combination arms with anti-EGFR (cetuximab) and anti-PD-1/PD-L1 in selected cancer indications. The rationale for combining BND-35 with cetuximab is supported by preclinical data and a thorough understanding of BND-35's mechanism of action. Specifically, BND-35 enhances antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. These processes are mediated by the binding of Fc receptors on immune cells to antibodies, such as cetuximab and other tumor-targeting antibodies. Each arm of the trial focuses on patient populations that are likely to benefit from ILT3/LILRB4 blockade based on translational research findings.

Professor Salomon Stemmer, M.D., a clinical investigator in the trial, emphasized the novelty of the combination therapy, which targets the immunosuppressive cell milieu within the tumor microenvironment. He highlighted the need for new treatments for cancers resistant to existing therapies and expressed optimism about BND-35's potential to overcome ILT3/LILRB4-mediated immunosuppression.

Tsuri Peretz, the project manager for the BND-35 program, explained that ILT3 is a unique receptor expressed on various suppressive myeloid cells within the tumor microenvironment. The binding of various ligands to ILT3 maintains the immunosuppressive state of the tumor microenvironment. BND-35 effectively blocks the interaction between ILT3 and its ligands, enhancing the immune system's ability to combat tumors. This results in increased physiological anti-tumor responses and improved destruction of tumor cells by immune cells.

BND-35 has shown promising results in in vitro and ex vivo studies, both as a monotherapy and in combination with anti-PD-1/PD-L1 pathway inhibitors and anti-EGFR agents. These studies demonstrated that BND-35 enhances the pro-inflammatory activity of various myeloid cells and inhibits the immunosuppressive activity of suppressive myeloid cells, thereby restoring T cell and NK cell activity.

Additionally, BND-35-induced immune activity enhancement was demonstrated in a unique system of patient-derived tumoroids. In vivo studies showed that blocking ILT3/LILRB4 activity with BND-35, either as a monotherapy or in combination therapy, led to decreased tumor growth and induced a pro-inflammatory phenotype in tumor-resident T cells and myeloid cell populations.

Biond Biologics is committed to developing advanced therapies targeting novel oncology pathways and enabling the intracellular delivery of biologics. Their other programs include BND-22 (SAR444881), an ILT2 blocking antibody partnered with Sanofi, and BND-67, an agent aimed at overcoming PD-1 pathway blockade resistance by attenuating CD28 shedding. The company is also developing INspire, a platform for the intracellular delivery of protein therapeutics.

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