Interview: An antibody that binds is just a starting point

Our latest interview with António Barroso, digs into how the right functional assay grounded in the right cell model, de-risks antibody discovery from lead selection through to IND.

Weighing reporter vs. primary-cell assays, early developability and manufacturability, and adapting assay design for next-generation formats.

An antibody that binds is just a starting point. The best antibody isn't the one that just binds, it's the one that also delivers the right biological effect. How early do you prioritize functional data in your antibody discovery programs?

We prioritize functional data as early as possible. Binding is necessary, but function is what ultimately drives therapeutic value. Integrating functional assays early helps identify antibodies with the right mechanism of action, reduces late-stage attrition, and ensures we optimize for biological relevance—not just affinity.

A functional assay is only as powerful as the cell model behind it. Every target has its own biology—ion channels, GPCRs, immune checkpoints—and the right cellular context can make all the difference. The question isn't just "Do you have a functional assay?" It's "Do you have the right model behind it?"

Definitely. A functional assay is only as predictive as the biological model it's built on. We start with the target biology and the intended mechanism of action. The ideal model should express the target at physiologically relevant levels, preserve the signalling pathways of interest, and reflect the disease context whenever possible. It's always a balance between biological relevance, robustness, scalability, and the specific questions the assay needs to answer.

Effector function can be evaluated using engineered reporter assays or primary cell–based assays. When selecting a lead candidate or generating data to support an IND package, how should these complementary approaches be integrated into the decision-making process, and what are the key strengths and limitations of each?

Reporter assays are excellent for high-throughput screening and consistency, making them ideal for early lead selection. However, they simplify biology may not fully capture the complexity of primary immune cell responses. For key development decisions and IND-enabling data, primary-cell assays provide the most biologically relevant evidence with reporter assays serving as complementary tools. However for reproducibility and ease of standardization, reporter system are well suited for QC applications such as potency testing and batch release during IND and clinical manufacturing. Therefore the key point is knowing when each one provides the evidence you need. When decisions involve selecting a lead candidate or building an IND package, biological relevance matters as much as assay performance.

A functional issue caught during lead selection is far easier to address than one discovered in the clinic. The best time to find a developability issue is before it becomes a development problem. Can you comment on this?

Absolutely. The earlier you identify functional or developability liabilities, the more opportunities you have to fix them. During lead selection, issues such as potency, stability, aggregation, or manufacturability can often be addressed through engineering or by selecting a better candidate. This also ties directly to early cell line development: evaluating expression levels, product quality, and manufacturability in a stable production cell line helps identify candidates that are not only biologically effective but also suitable for scalable manufacturing. Running cell line development in parallel with lead selection helps identify manufacturability liabilities early and avoid costly redesigns, delays and increased development risk.

As pipelines increasingly shift toward novel antibody formats—such as bispecifics, ADCs, and other next-generation therapeutics—functional assays need to evolve as well. How do you adapt your assay design to these modalities, and what are the biggest challenge? 

The starting point is always the mechanism of action. Novel formats such as bispecific and ADCs require assays that capture their unique biology, whether that's dual-target engagement, immune cell recruitment, internalization, payload activity, or targeted cell killing. Rather than adapting a conventional antibody assay, we design fit-for-purpose assays that reflect the intended therapeutic function. The biggest challenge is developing models that are both biologically relevant and robust enough to support discovery, development, and ultimately QC, while ensuring the readout is predictive of clinical performance.