Speed-to-IND Starts with Toxicology: A Rapid-Fire Q&A with Lonza

*Full transcript available below

In a rapid-fire Q&A interview, Michael De Marco, PhD, head of commercial development Integrated Biologics, Lonza, shares expert insights on how early toxicology strategies can accelerate biopharmaceutical development.

The rapid-fire interview accompanies a longer form discussion with BioPharm International®, in which Dr. De Marco explores the role of early tox data in building investor confidence, overcoming tox material scale-up challenges, integrating emerging preclinical technologies, and leveraging contract development and manufacturing organization (CDMO) partnerships to reduce risk and speed programs toward investigational new drug (IND) submission. These aspects are key considerations for small and emerging biotechnology companies navigating today’s compressed development timelines.

BioPharm: How does early completion of toxicology studies influence investor confidence and funding opportunities?

Dr. De Marco (Lonza): In today’s environment, small and emerging biotechs are under constant pressure to advance molecules from lab to clinical trials faster than ever before. Toxicology (tox) studies are a critical milestone toward securing regulatory clearances such as IND and/or clinical trial application (CTA) status, both of which are crucial for some biotech to securing further funding and strategic partnerships.

Tox studies are essential for assessing the safety and efficacy of new treatments prior to first-in-human trials. They help minimize risks to participants, provide insights into the biological mechanisms of action, and enhance the scientific credibility of the candidate molecule. By delivering a rigorous assessment of safety and behavior, early tox data not only protect patients but also build investor confidence, often serving as a strategic investment that supports additional funding and accelerates a program’s path to the clinic.

What are the key challenges in scaling up production of tox materials?

Accelerating the scale-up of tox materials production involves navigating a complex landscape of challenges, including maintaining stringent quality control, ensuring process consistency, and managing supply chain and regulatory requirements. Overcoming these hurdles requires striking a careful balance between speed, compliance, and product quality to generate tox materials that are representative of the final product entering the clinic, while adhering to compressed timelines.

To address these challenges, companies need to establish robust systems and processes that can withstand the pressures of rapid tox material generation. This includes establishing robust processes and quality management systems that help mitigate these challenges. Companies must also employ the right technologies and establish a solid process development foundation to ensure successful manufacturability.

These technologies and processes include using scalable expression systems that guarantee higher titer and stability, which are crucial for efficient production, and using upstream and purification processes designed with manufacturability in mind. By focusing on these areas, companies can optimize their production processes, reduce inefficiencies, and enhance the overall quality and consistency of their biopharmaceutical products.

Early assessment of a product’s manufacturability and immunogenicity is another critical area that requires attention as it helps reduce candidate risk by spotting potential production problems and immune reactions before the development activities start. For example, manufacturability assessments evaluate chemical degradation pathways, post-translational modifications, and physical stability factors, such as protein aggregation. Immunogenicity assessments leverage in-silico and in-vitro screening tools to identify T-cell epitopes that may trigger unwanted immune responses.

Collaboration with experienced partners, such as a CDMO with integrated end-to-end solutions, including robust platform processes, analytical capabilities and strong supply chain infrastructure, can help small and emerging biotech companies reduce risks and bottlenecks for regulatory success.

How can advanced technologies, such as in-silico modeling and iPSC-derived systems, be integrated into preclinical development to enhance tox assessments?

[In December 2025], FDA announced the phase-out of animal testing requirements for monoclonal antibodies (mAbs) and other drugs, shifting to adoption of new approach methodologies (NAMs), such as organ-on-a-chip systems, computational modeling, and advanced in-vitro assays over the next years (1). These NAMs offer a promising solution to reduce costs, improve predictive accuracy, and minimize the reliance on animal models.

As a result, in silico tools and induced pluripotent stem cell (iPSC)-derived systems are becoming increasingly important in preclinical development. For example, in-silico approaches for toxicology studies utilize advanced computational techniques to predict the toxicological profiles of compounds, therefore, reducing the need for animal testing. Key in-silico methods include physiologically-based pharmacokinetic modeling, quantitative systems pharmacology modelling and in-silico off-target screening. Together, these approaches offer a powerful alternative to animal studies by using data analytics and modeling to predict safety, efficacy, and pharmacology outcomes that are relevant to humans.

Similarly, the power of iPSC-based systems derives from the ability of iPSCs to differentiate into a variety of cell types, enabling researchers to study specific organ toxicities. These systems also support high-throughput screening and can help reduce the need for animal testing.

These approaches are still in the early stages and require further validation before they can be fully integrated into regulatory practices. Consequently, traditional animal toxicology studies continue to be the ‘gold standard’ providing the most reliable and widely accepted data for safety assessments. Until these NAMs are fully validated and widely accepted, animal studies remain essential for ensuring the safety of new compounds.

What role do CDMO collaborations play in expediting the delivery of tox materials?

Efficient production of tox materials goes beyond technical expertise; it demands a robust infrastructure capable of supporting rapid scale-up, thorough analytical testing, and comprehensive documentation under strict quality standards. A CDMO with these capabilities, combined with flexibility in chemistry, manufacturing, and controls strategies, can help streamline the process for drug developers and keep programs on schedule.

For example, CDMOs deploy integrated development and manufacturing teams that can execute multiple activities in parallel, such as process optimization, formulation, and analytical method development, while simultaneously producing the required materials. This capability is particularly valuable when project timelines are tight. CDMOs with strong technical and regulatory expertise can also guide IND-enabling studies and ensure that tox batches meet data standards suitable for regulatory submission.

Ultimately, initiating toxicology studies as early as possible is one of the most effective ways to minimize delays in IND submissions, and that depends on the early availability of tox-grade material. Selecting a CDMO partner with established platform processes, mature quality systems, and integrated capabilities is key to accelerating material readiness and ensuring program success.

Small and emerging biotechs also increasingly recognize the value of partnering with a CDMO that offers the added benefit of integrated drug substance and drug product programs for any molecule type, ensuring a smooth and compliant development pathway. A comprehensive package that enables the expression of early-phase material in a scalable, good manufacturimg practice-ready cell line can further accelerate timelines and enhance molecule understanding.

About the speaker

Michael De Marco, PhD, Vice President, Commercial Development, Integrated Biologics, Lonza

Dr. De Marco brings extensive experience in the chemical and biotechnology industry, with a proven track record of driving innovation and executing strategies that support business growth. Before joining Lonza, Dr. De Marco held various positions at BASF and served on the board of directors for Corbiota. He studied at the University of St. Gallen and earned his doctorate in chemistry from Justus Liebig University Giessen.

Transcript

Editor's note: This transcript is a direct, unedited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Speaker 1

Hi, I'm Michael De Marco. I'm heading commercial development within monsters, integrated biologics platform. Tox studies do more than just a safety assessment. They can be a very strategic investment in the company's future, because strong tox data help to establish the scientific credibility and the regulatory readiness of a program for the IND phase or a clinical trial application. Those are key milestones for investors, and give them confidence that they are willing to provide further funding and therefore advance the development of the programs.

accelerating tox material production faces in my eyes numerous challenges. One is maintaining quality and process consistency. The other is then managing the supply chain and regulatory complexity. So success requires therefore well established process platforms and the right technologies to strike the right balance between speed, compliance and product quality together, these approaches then ensure that we generate materials that are representative of the final product entering the clinical while meeting tight development timelines for next generation Biotherapeutics.

Strategies shift more into the direction of addressing their added complexity. It's about using advanced analytics early to quickly understand unique quality attributes, applying high throughput formulation screening to tackle stability challenges and developing flexible processes. And that includes also downstream steps that cannot be adapted to non standard formats. We have efficient gene assembly and Sunline development, they are both key for generating representative material quickly.

By partnering with a cdmo, you benefit really from robust infrastructure, integrated capabilities and the regulatory expertise. Such partnerships enable you to be efficient, fast and compliant in production of these tox materials, what is essential to accelerate the drug development timelines.

Reference

1. FDA. FDA Releases Draft Guidance on Reducing Testing on Non-Human Primates for Monoclonal Antibodies. Press Release. Dec. 2, 2025.