Hu-VHH Antibody Assets

Exploring New Opportunities of Biocytogen's Hu-VHH in Multi-Specific Antibodies, ADCs, and Cell Therapies

The single VHH domain (~12-15 kDa), which allows for better penetration of solid tumors and the blood-brain barrier, represents a promising diagnostic and therapeutic approach.

Biocytogen's RenNano Mice: A Fully Human Heavy Chain-Only Platform for VHH Discovery

RenNano mice were developed via genetic modification of the antibody constant region in RenMab mice. Following immunization, RenNano mice produce fully human heavy-chain-only antibodies (HCAbs) that can bind to antigens without a light chain. RenNano-derived HCAbs possess diverse CDR3 sequences and can recognize a variety of epitopes with excellent specificity and affinity. HCAbs derived from RenNano mice demonstrate robust biological function both in vitro and in vivo, making them suitable for various drug modalities, including bispecific antibodies, multispecific antibodies, ADC and cell therapies. Using RenNano mice, Biocytogen initiated the "Nano 100 Project" in February 2023 to discover fully human therapeutic VHHs against over 100 different targets.

RenNano Platform Related Antibody Library

Case Study 1: Selective Assets for TFR1-TOP HCAbs

CD71, also known as TFR1 (Transferrin receptor), a single transmembrane, mainly transports Fe ions into cells by binding to Transferrin TF (Transferrin). Anti-TFR1 antibody are widely used as BBB shuttle.

TFR1-TOP Antibody demonstrated better BBB penetrance efficacy and advantage in in vivo.

• Better BBB penetrance performance than benchmark antibody.
• Monovalent perform much better BBB penetrance than Bivalent form.
• Flexibly suited for non-conjugation shuttling (e.g. fusions or bsAbs) or conjugated payload shuttling (e.g. AOC or small molecules).

Better BBB penetrance than Benchmark

Monovalent vs. Bivalent

Case Study 2: Selective Assets for VEGF-A HCAbs

• VEGFA (or VEGF hereafter) is the prototypic member of a family that also includes placental growth factor (PLGF, also known as PGF)、VEGFB、 VEGFC、 VEGFD.
• VEGFA is highly expressed in various cancer cells, thease include lung cancer, breast cancer, gastrointestinal tract, renal and ovarian carcinomas.
• Indications: Metastatic colorectal cancer, advanced/metastatic or recurrent non-squamous non-small cell lung cancer, recurrent glioblastoma, hepatocellular carcinoma, renal cell carcinoma, uterine cervix cancer, ovarian cancer.
• Benchmark: Bevacizumab-analog
• Our anti-VEGFA monoclonal antibodies from RenNano mice have better blocking activity than benchmark.

Affinity and blocking activity

Case Study 3: Selective Assets for DLL3 HCAbs

• Delta-Like Ligand 3 (DLL3) is a negative regulator of Notch signaling.
• DLL3 is aberrantly expressed on the cell surface in the majority of NEPC and other small cell carcinomas.
• Indications: SCLC, NEPC, neuroendocrine carcinoma.
• Benchmark: AMG-757-analog
• Our anti-DLL3 monoclonal antibodies from RenNano mice have good binding properties with SCLC cells and diverse binding epitopes.

Good binding properties in tumor cells

Epitope binning assay

Binding site description	Number
DSL domain	1, Rova-T-analog
EGF-like3	AMG-757-analog
EGF-like4-6+proximal membrane	4
N-terminal initiation site	2

Biocytogen is actively seeking collaborations with global pharmaceutical and biotech companies in VHH-related therapeutics, such as cell therapies, BBB shuttles, bispecific and multi-specific antibodies, ADCs and RACs, to develop novel drugs with first-in-class and/or best-in-class potentials.

For co-development or licensing inquiries, contact us today!