Infinimune's Dr McDonnell on How Converging Human-Based Technologies Are Defining the Next Era of Clinical Development

In the second segment of an interview with Infinimmune CEO and co-founder Wyatt McDonnell, PhD, Dr McDonnell addresses why human-derived antibodies offer structural advantages over humanized animal-derived molecules, and how converging technologies are reshaping the antibody development pipeline. Dr McDonnell spoke with BioPharm International® about his presentation in the session, “Beyond Animal Testing: How Organoids and Human-Based Models Are Transforming Drug Discovery,” at the 2026 BIO International Convention (BIO 2026).

Dr McDonnell stresses that the risk of humanizing animal-derived antibodies is frequently underestimated. Antibodies are large, complex proteins in which the relationship between sequence, structure, and function is highly sensitive. Engineering residue changes during humanization of non-human-derived antibodies introduces a real failure rate, he notes. Human-derived antibodies, however, carry native heavy and light chain pairing, natural affinity maturation, and germline-encoded developability properties from the outset, he explains.

How are single-cell genomics, organoids, and AI converging to replace animal models in antibody development?

Dr McDonnell identifies 3 enabling technologies driving this shift: single-cell genomics for interrogating human immune responses at individual cell resolution; organoid and organ-on-chip platforms for testing drugs in human tissue context; and artificial intelligence (AI) models trained on large-scale human datasets capable of predicting affinity, specificity, manufacturability, and half-life from sequence alone, before any recombinant protein is synthesized.

"For complex biologics, where small changes in sequence can mean the difference between a drug and a development failure, having that human-relevant data at every stage isn't just a nice-to-have, it's also risk mitigation," Dr McDonnell states. “So, I think we're heading toward a model where human data is the default at every stage.”

He also says that animal studies should become the exception, reserved for questions that cannot be answered any other way, a direction he describes as consistent with FDA's current regulatory roadmap. Companies that integrate these tools into a coherent pipeline, rather than adding them onto a fundamentally animal-derived workflow, will define the next era of clinical development, he emphasizes.

Watch the first segment of his presentation-based interview, and catch up on his other BIO 2026 interviews by clicking here for segment 1 and here for segment 2. Click here for more conference coverage.

BIO 2026 occurred June 22–25 in San Diego.

About the speaker

Wyatt McDonnell, PhD, CEO and Co-Founder, Infinimnune

Dr McDonnell also serves as chairman of Infinimmune, a biotechnology company pioneering antibody discovery and design by leveraging natural human immunity to develop safer and more effective therapeutics for complex diseases. Under his leadership, Infinimmune has established strategic collaborations with Merck, Immunome, and GRID Therapeutics to advance the discovery and development of novel antibody therapeutics. Previously, Dr McDonnell helped develop 10x Genomics’ first therapeutic antibodies and core immunology intellectual property behind three commercial products. He has co-authored 31 peer-reviewed publications, including in Nature, Cell, and Nature Medicine, and is an inventor on 19 published patents. Dr McDonnell earned a PhD and Master of Science from Vanderbilt University School of Medicine.