Scaling Biologics with Early De-risking Package: Integrated Developability & Expression Q&A

For emerging biotech companies, what are the most common challenges you see when they begin developing a new molecule?

RD: Emerging biotechs often face three interconnected hurdles early on:
(1) unseen sequence liabilities, such as Post-Translational Modification (PTMs), aggregation sites or immunogenic motifs, which may only surface during IND-enabling work if not screened earlier;
(2) limited translational confidence, especially when early data are generated in non-commercial or non-CHO platforms, leading to surprises when transitioning into manufacturing; and
(3) funding pressure, where investors expect a clear, data-driven risk assessment—often underpinned by early immunogenicity testing. Early de-risking aligns scientific rigour with stakeholder expectations, making it a cornerstone of in silico drug development that prevents costly rework and supports stronger valuation at key decision points.

From your experience, which early scientific insights have the biggest impact on shaping the direction of a molecule’s development?

RD: Three insights consistently shape the trajectory:
(i) In silico identification of key developability risks (immunogenic epitopes, PTMs, aggregation hotspots);
(ii) early manufacturability signals generated directly in the GS® CHO expression system, ensuring data relevance and reducing later surprises; and
(iii) early immunosafety indicators, particularly PBMC* cytokine storm potential or donor variability patterns. Combined, these insights enable confident prioritisation and minimisation of downstream technical and clinical uncertainty.

How can early development services influence the decisions scientists make when prioritising or refining candidate molecules?

YS: By integrating in silico risk prediction, CHO-based expression and in vitro immunogenicity assessment scientists receive decision-ready evidence rather than isolated datapoints. This consolidated approach accelerates ranking, flags liabilities earlier and helps inform the next development steps. The overarching results also support internal governance and investor presentations, enabling quicker, aligned go/no-go decisions.

What practical benefits can customers gain from using in silico developability assessments at this stage?

MH: These assessments are low-cost, fast and high-impact, assessing manufacturing and immunogenicity developability risks. Highlighted manufacturing liabilities include PTMs, aggregation risk, charge distribution, and chemical liabilities such as oxidation or clipping. Immunogenicity risks are also identified using our T cell epitope prediction software, including proprietary filters to reduce false positives. Both manufacturability and immunogenicity assessments are tailored to support customers with actionable clarity on the candidates to prioritise for expression and immunosafety testing.

Can you evaluate multiple sequence variants, and how do you rank them for developability?

MH: Yes—our in silico workflows support parallel evaluation of anywhere from a single candidate to 100s of sequences. Ranking incorporates multi-parameter scores across manufacturability and immunogenicity and provides an overall risk score. These tools are designed to give a manufacturing developability context to derisk and select candidates at the earliest opportunity, saving time and expense downstream.

How do in silico analyses integrate into the broader de-risking package and support downstream decision-making?

MH: They serve as step 1 in the Early De-risking Package, providing an initial developability assessment that guides the lower risk molecules to advance to CHO expression and PBMC-based immunogenicity screening. Outputs help determine whether a liability needs immediate engineering, can be monitored downstream, or is acceptable based on risk–benefit. Working with our colleagues in expression and immunosafety we provide integrated reporting to create a unified risk picture bridging sequence, manufacturability and patient safety.

What practical benefits can customers gain from small scale expression in early development stage?

RM: Early material generated in the GS® CHO system provides manufacturability evidence directly relevant to future GMP production. Customers gain titre, product assembly, aggregation behaviour and mass data, plus material for in vitro and in vivo studies. Generating this data early avoids repeating assays once CLD begins and strengthens confidence in the molecule’s viability.

Are you able to express different types of molecules, and how flexible is this approach for diverse formats?

RM: Absolutely. Lonza’s GS® platform has expressed 2000+ products, spanning mAbs, bispecifics, fusion formats, Fc-fusions, fragments, multi-chain constructs and recombinant proteins. Over 50% of molecules expressed in 2025 were non-mAbs, demonstrating strong format flexibility.

This flexibility is further strengthened by Lonza’s GS Ori-Go™ vectors, which support diverse and complex molecule types while enabling high titers, improved stability, and a more streamlined development process, helping accelerate timelines and reduce hands-on effort.

How does the expression data contribute to the overall de-risking package?

RM: Expression data validates manufacturability predictions and highlights real-world performance: titre, chain pairing, PTMs, aggregation levels and stability. When combined with in silico and immunogenicity assay findings, it forms a triad of evidence supporting case-by-case decisions—proceed, engineer, monitor or replace.

What practical benefits can customers gain from immunogenicity testing in early development stage?

NS: PBMC-based immunogenicity assays are high throughput, cost effective, and better replicate human innate and adaptive responses compared to traditional animal models. This allows for early risk identification (e.g., during the lead selection phase), which in turn can help to prevent downstream attrition and inform the next stages of development. Customers gain insight into cytokine storm potential, off-target activation, ADA-related T cell mechanisms, and innate immune responses to impurities.

Why was the in vitro PBMC activation assay selected for this de-risking package over other immunogenicity assays?

NS: The PBMC activation assay evaluates the risk of cytokine storm, which directly correlates to the risk of patient safety. Our standard cytokine panel used to screen test products is aligned with the latest regulatory expectations and captures a wide variety of innate immune signaling pathways.

How do in silico predictions, early expression, and immunogenicity data come together to provide a clearer picture of a molecule’s overall potential?

YS: Each dataset answers one of two central questions— “Can the molecule be produced?” and “Is it safe for patients?”—combining manufacturability data from CHO GS® expression with immunosafety insights and in silico risk to produce a clear, consolidated assessment.

Where do you see the biggest time savings for emerging biotechs when they use an integrated early evaluation approach like the early de-risking package?

RD: For emerging biotechs, the biggest time savings come from what the integrated data allows them to avoid. When sequence liabilities, manufacturability barriers, and immunosafety risks are clarified early and in combination, teams can make confident decisions faster—whether that means advancing a strong molecule, further optimizing a promising candidate or stepping away from one that would stall later.

What typically becomes the next step in advancing a biologic candidate after completing the de-risking package?

RD: Depending on outcomes: proceed to CLD using optimised vectors, perform targeted optimisation to resolve flagged risks, or plan IND-enabling studies informed by the integrated data and recommendations.

YS: Beyond the de-risking bundle, broader EDS services can support next steps through flexible, modular offerings, including, expanded immunosafety testing, larger scale non-GMP material supply (perhaps expressing sufficient amounts for in vivo efficacy work), or, pending the outcome of the de-risking bundle, protein engineering to mitigate any identified risks and improve the developability of the molecules. These services allow emerging biotechs to continue de-risking and strengthening their molecule strategically, adding value, without duplicating earlier work.