VHH Discovery Platform

Unlocking High-Performance VHH Antibodies Through FC8TM and Immune Discovery Routes

At Cortalix, VHH discovery is the foundation of everything we develop. Every discovery campaign starts within our proprietary FC8TM scaffold framework, humanized, thermally and pH-stable, and aggregation-free by design, so the binders that come out are already built for clinical translation.

We combine FC8TM synthetic discovery, powered by ribosomal display and phage display, with immune library discovery, to deliver fast, reliable, and application-ready binders for imaging, therapeutics, diagnostics, and cell-based engineering.

FC8™ Synthetic Discovery: Ribosomal Display + Phage Display

Our primary discovery route, and the fastest path to a clinical-ready lead. Every campaign starts within the FC8TM scaffold, screened first through ribosomal display across a functional diversity of up to 1014 variants, then carried seamlessly into phage display for precise enrichment and selection.

Key advantages:

  • Immediate project start, no immunization required
  • Up to 1014 functional diversity via ribosomal display
  • Engineered for solubility, stability, and >90% humanization
  • Ideal for toxic, non-immunogenic, or difficult antigens
  • Highly controlled design enabling efficient downstream engineering
Workflow VHH nanobodies panning

The Cortalix discovery workflow combines FC8™ synthetic and immune VHH libraries with phage display. After multiple rounds of phage panning and screening, including optional assays on intact cells, unique binders are identified. Clones are validated by ELISA-based affinity measurements and DNA sequencing to ensure optimal candidates for downstream development.

Immune Library Platform

Cortalix maintains high-quality immune VHH libraries generated from immunized llamas or alpacas, coordinated by Cortalix and performed at certified partner facilities. This route is preferred when affinity, specificity, or complex target recognition is essential.

Strengths:

  • Naturally affinity-matured binders
  • Broad epitope coverage
  • Excellent performance on membrane proteins and complex targets
  • High success rate for advanced or conformational epitopes

CDR Grafting & Framework Optimization

When top binders come from immune libraries, CDRs can be grafted onto our FC8TM framework.

Benefits:

  • Improved humanization
  • Increased stability and expression yield
  • Consistent performance across downstream engineering steps

This ensures every final VHH binder is both biophysically robust and ready for translation.

Why Use These Platforms?

  • Combining FC8TM synthetic and immune library discovery provides:
    • Maximum epitope coverage
    • Higher probability of success across antigen classes
    • Superior diversity and binder quality
    • Flexible project design tailored to the target

    This dual‑platform approach strengthens downstream applications such as MultiDome™ multispecifics, AlbuFlex™ half‑life extension, and CARVex™ nanobody-based CAR-T targeting.

Discovery Workflow

Our standard discovery workflow includes:

  • Antigen QC & preparation

  • Library selection (FC8TM synthetic, immune or hybrid)

  • Phage display panning — including optional cell-based panning

  • High-throughput clone screening

  • Binding validation (ELISA/BLI)

  • Sequence analysis & developability assessment

  • Optional reformatting (bivalent, Fc-fusion, NIR-labeling)

The entire workflow is modular and can be adapted to any project design.

Deliverables

Typical project outputs include:

  • Validated VHH antibody sequences

  • Purified VHH proteins (optional)

  • Full binding dataset and QC report

  • Developability assessment

  • Optional reformatting into bivalent, trivalent, Fc-fusion, or imaging-ready constructs

From Discovery to Application

VHHs generated in this platform seamlessly feed into Cortalix’s engineering suite:

  • MultiDome™ Multispecific engineering

  • AlbuFlex™ Albumin-binding half-life extension

  • CARVex™ VHH-based CAR-T targeting

  • NIR imaging probes

  • Assay and ELISA development

This ensures a smooth path from binder discovery to translational application.

Tailored for Industry and Academia

Cortalix provides flexible partnership structures, ranging from fee‑for‑service projects to collaborative programs. Our Discovery Platform is designed for:

  • Biotech and pharma target discovery programs

  • Imaging probe development groups

  • CAR‑T and cell therapy teams

  • Translational research institutes

Start your VHH discovery project

Contact us to discuss your target, project design, or antigen strategy. We help you select the optimal discovery route, synthetic, immune, or a hybrid approach, to ensure strong outcomes and fast progression toward application-specific engineering.

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