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Bispecific Antibody & Multispecific Format Engineering

The Right Format for the Right Mechanism of Action
Overview
HCAb Engineering
Optimization
Development

Expanding the Potential of Next-Generation Antibodies

Nona Biosciences offers specialized solutions in bispecific and multispecific antibody engineering, addressing the complex challenges associated with next-generation therapies. To ensure the success of these advanced modalities, we provide end-to-end support, from antigen preparation to developability assessments, enabling seamless candidate profiling to assess and de-risk the development process. Utilizing heavy chain-only antibody (HCAb) engineering and Harbour Mice® technology, we produce fully human antibodies with excellent stability, solubility, and low immunogenicity. Compared to camelid-derived VHH domains, Nona’s HCAbs retain all the advantages of small antibody formats while being fully human, highly druggable, and less immunogenic, providing a stronger starting point for therapeutic development.

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Innovating Antibody Formats with HCAb Engineering

Our engineering capabilities leverage the flexibility of heavy chain-only antibodies (HCAbs) to create tailored geometries and novel mechanisms of action, while naturally sidestepping common pitfalls such as light-chain mispairing. These HCAb-based designs allow us to address resistance mechanisms like pathway downregulation, crosstalk, and alternative pathway upregulation with greater freedom.
 
We extend our expertise to include VH domains and VHH domains (nanobody formats), along with other antibody fragments such as scFv. These formats enable advanced engineering of bispecific and multispecific antibodies and next-generation constructs with improved stability, epitope accessibility, and therapeutic efficacy. This strong foundation in bispecific engineering has also allowed Nona to develop HBICE®, our platform dedicated to immune cell engagement, and through our innovative approaches to advance into next-generation modalities such as mRNA-encoded bispecifics. For a more detailed look at our workflows and HBICE® applications, see our Scientific & Engineering Insights on HCAb-Based Bispecific Engineering.
Innovative Platforms for Bi- and Multispecific Development
mRNA-LNP
mRNA-LNP encoding technology
Immune Cell Engagement Platform
Engineering Highlights:

  • Innovative Designs:
    Simplify development with HCAbs, avoiding light chain mismatches and enabling flexible geometries.

  • Enhanced Functionality:
    Tailor binding valences, geometries, and relative positions to optimize therapeutic efficacy.

  • Streamlined Manufacturing:
    High recovery rates and fewer complexities reduce production timelines.

Format Screening & Optimization

Nona’s modular antibody platform allows for the systematic screening of bispecific and multispecific constructs through a stepwise permutation approach. Rather than relying on pooled or high-throughput format mixing, we carefully test and compare variable elements such as binder position, Fc geometry, valency, and spatial orientation one at a time. This data-driven strategy ensures early identification of the most promising constructs, improving stability, manufacturability, and function, setting the stage for efficient downstream development.

Preclinical Development

Even after optimal format selection, bi/multispecific antibodies present distinct development challenges including light chain pairing mismatches, dual-target binding stability, and complex post-translational modifications. Our HCAb-based formats are engineered to avoid these pitfalls from the outset, simplifying production and reducing downstream variability.

To ensure only the most viable candidates advance, we apply a rigorous combination of developability analytics and in vivo validation. Early-stage stress testing, predictive assays, and PK/PD studies provide critical insights into manufacturability, safety, and overall therapeutic potential.

Our Preclinical Evaluation Capabilities:
  • Stress Testing:
    Freeze-thaw, pH variation, temperature extremes
  • Analytical Profiling:
    SEC-HPLC, LC-MS, ELISA

  

  • Stability & Immunogenicity:
    UNCLE and orthogonal assays
  • In Vivo Characterization:
    Mouse efficacy, PK/PD, monkey tox, tissue cross-reactivity

Work With Nona to Deliver the Next Generation of Antibodies

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Explore Related Resources

Bispecific Engineering Technical Analysis
HBICE® Immune Engagement
Antibody Engineering
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