Preclinical Data on the Potential of Byondis ADC BYON3521 Published in Molecular Cancer Therapeutics

• BYON3521 Targets c-MET, Overexpressed in Solid Tumors
• ADC Currently in a First-in-Human Study

NIJMEGEN, Netherlands, April 12, 2023 /PRNewswire/ -- Byondis B.V., an independent, clinical-stage Dutch biopharmaceutical company creating precision medicines, today announced that Molecular Cancer Therapeutics (an American Association for Cancer Research journal) has published encouraging preclinical data on its investigational, next generation antibody-drug conjugate (ADC) BYON3521.

The article, "Preclinical profile of BYON3521 predicts an effective and safe c-MET-antibody-drug conjugate," suggests that BYON3521 has an encouraging safety/efficacy window with potential for clinical benefit in patients. A First-in-Human dose escalation study is currently ongoing to determine the maximum tolerated dose and recommended dose for expansion (NCT05323045). The study is enrolling patients in leading oncology centers in Belgium, Italy, the Netherlands and the United Kingdom.

The data from in vitro and in vivo studies showed that BYON3521 potently and selectively kills tumor cells expressing c-MET, even at low c-MET-expressing levels. In addition, the nonclinical safety evaluation showed that BYON3521 is well tolerated, predicting a substantial clinical therapeutic window.

"The c-MET/HGF pathway is one of the most dysregulated pathways in human solid tumors and is generally associated with a poor prognosis," said Byondis Chief Scientific Officer Wim Dokter, Ph.D. "Being able to use that pathway to deliver clinical benefit to patients will therefore be extra rewarding."

c-MET (also called tyrosine-protein kinase MET [Mesenchymal Epithelial Transition] factor or HGFR [Hepatocyte Growth Factor Receptor]) is a receptor expressed on the surface of epithelial cells of many different organs. Binding of the growth factor HGF to c-MET leads to normal cell division, growth and differentiation, important in the generation of new tissue, e.g., during the development of a fetus, or during growth or wound repair.

But in many tumor cells, c-MET activation is dysregulated: too much c-MET is expressed, c-MET is mutated or c-MET is active even without the binding of HGF. c-MET is overexpressed in a variety of solid tumors, such as renal cell cancer, uveal (ocular) melanoma, non-small cell lung cancer and head and neck squamous cell cancer.

BYON3521, a Next Generation Antibody-Drug Conjugate

BYON3521 is comprised of the humanized IgG1 c-MET-targeting monoclonal antibody, SYD2884, and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA or SYD980). The antibody part of BYON3521 binds to c-MET on the surface of the cancer cell and the ADC is internalized. After proteolytic cleavage of the linker in the lysosome, the inactivated cytotoxin is activated, binds to the DNA and DNA damage is induced, eventually resulting in tumor cell death. BYON3521 is considered a form of targeted chemotherapy.

Byondis' Distinctive, Proprietary Linker-Drug and Site-Specific Conjugation Technology

BYON3521 incorporates Byondis' distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine® and its site-specific conjugation technology ByonShieLD®. The characteristic design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower or no c-MET expression may improve the efficacy potential through the so-called bystander effect.

About Byondis

Driven to improve patients' lives, Byondis is a privately held, Dutch clinical-stage biopharmaceutical research and development company creating precision medicines targeting intractable cancers and autoimmune diseases. Byondis' broad development portfolio comprises targeted and immuno-oncology (IO) therapies in preclinical, early- and late-stage clinical phases. These candidates combine Byondis' expertise in linker-drug (LD) technology, antibody-drug conjugation, targeted cytotoxic therapy, and monoclonal antibody (mAb) development. Byondis designs and produces next generation antibody-drug conjugates (ADCs), as well as mAbs and new chemical entities (NCEs) that can stand alone or be incorporated in its ADCs.

Byondis has a dedicated team of more than 400 employees, including highly educated scientists and skilled technicians working in state-of-the-art R&D laboratories and Good Manufacturing Practice (GMP) production and conjugation facilities on its campus in Nijmegen, the Netherlands. The company collaborates with other global biotechnology and pharmaceutical companies and many leading academic research institutions. For more information, visit www.byondis.com.

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