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ADC Development and Linker Payload Innovation

Advanced conjugation and CMC-enabling characterization across conjugated modalities

Overview
Discovery
Conjugation
Characterization

Proprietary Linker–Payload Innovation for Differentiated ADCs

Nona Biosciences has developed a patent-protected proprietary linker–payload platform incorporating a topoisomerase inhibitor, engineered specifically for next-generation antibody–drug conjugates. This innovation enables intra-tumor drug release through tumor microenvironment (TME)-responsive cleavage, providing a differentiated mechanism of action that extends beyond conventional internalization-dependent approaches. By enabling payload release within both the TME and cancer cells following tumor-specific enrichment, it supports more effective and targeted cytotoxic activity.

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Flexible Formats & Precise Targeting
TME-Responsive Linker
Proprietary Topo Payload

Fully Human Discovery Platform

Nona’s fully human antibody discovery platform enables the identification and engineering of antibodies optimized for conjugated therapeutics. Through Harbour Mice® technology, Nona provides access to both conventional H2L2 antibodies and heavy-chain-only antibodies (HCAbs), supporting diverse antibody formats and targeting strategies for ADC development. This HCAbs further enhance conjugate design through improved tissue penetration, access to unique epitopes, and compatibility with site-specific conjugation strategies.

HCAb Feature Development Advantage
Smaller size (~85 kDa) Better tissue penetration
Unique epitope access Better specificity Better internalization
Compatibility with site-specific DAR2 conjugation High homogeneous product High stability with conserved disulfide bonds
Fully human antibody sequences No additional tags No non-natural amino acids No changes to glycosylation patterns
Simplified conjugation design Improved manufacturability
Flexibility Expandable to other modalities (e.g., bispecific antibodies)

These discovery capabilities integrate seamlessly with downstream conjugation and characterization, enabling efficient progression from target identification through ADC development.

Advanced Conjugation Technologies

Nona’s conjugation technologies are designed to support both proprietary linker–payload programs and client-defined strategies across diverse conjugated modalities. Conjugation workflows are scalable from early discovery through gram-level production and are optimized to balance stability, release behavior, and manufacturability.

Designed for flexibility, Nona supports customized linker–drug design and conjugation strategies tailored to specific therapeutic requirements. Each design is optimized for stability, release behavior, and manufacturability, informed by payload mechanism, tumor-associated proteases, and conjugation chemistry.

Customized Linker–Drug Design

Conjugation Capabilities:
  • Support for client-provided, commercially available, and custom-designed linker–drug constructs
  • Cysteine- and lysine-based conjugation strategies across antibodies, peptides, and oligonucleotides
  • Adaptable workflows across payload classes and target biology

HCAb DAR2 Site-Specific Conjugation Platform

DAR2 enables precise, site-specific drug attachment with a consistent drug-to-antibody ratio of two. This control enhances stability and therapeutic index while avoiding the liabilities of conventional high-DAR species, providing a reproducible and manufacturable path for ADC development.

  • It will shorten the workflow for positive plasma cell screening from months to a single day.

  • The high throughput screening with 14K or 20K chips dramatically decreases labor costs for screening more than 10,000 cells.

  • Direct screening with individual plasma cells prevents the diversity loss/bias during hybridoma screening.

  • It will shorten the workflow for positive plasma cell screening from months to a single day.

  • The high throughput screening with 14K or 20K chips dramatically decreases labor costs for screening more than 10,000 cells.

  • Direct screening with individual plasma cells prevents the diversity loss/bias during hybridoma screening.

CMC-Enabling ADC Characterization

Our ADC solution provides full-spectrum physicochemical and biological characterization to support CMC-enabling development decisions and preclinical readiness, including developability assessment of ADCs and other bioconjugates. Integrated in vitro and in vivo workflows validate and de-risk conjugation strategies while supporting scalable manufacturing, batch consistency, and regulatory readiness.

A comprehensive suite of analytical methods supports these capabilities, including:

  • Physicochemical Characterization:
    Analytical tools such as LC-MS, SEC-MALS, and cIEF offer detailed insights into charge heterogeneity, molecular weight, DAR, conjugation stability, aggregation, and free drug residue monitoring.
  • In vitro Validation:
    Bioactivity studies include antigen binding, internalization, soluble antigen interference, cytotoxicity, and bystander killing.
  • In vivo Validation:
    Pharmacological models encompass PK studies, stability assessments, and efficacy testing in CDX, PDX, and heterogeneous tumor environments.

Attribute Analytical Methods
DAR HIC
UV
mass spec
RP-HPLC
Purity SEC (HMW & LMW species)
HIC (DAR0 content)
RP-HPLC (DAR0 content)
Residual free drugs RP-HPLC
Endotoxin Chromogenic LAL assay
Recombinant Factor C assay

Let’s Conjugate the Right Solution

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Explore Related Resources

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