Despite the clear potential of hybrid peptide-antibody drugs, their development is slow. This is attributed to human nature in science: researchers tend to stick with familiar, comfortable modalities and the tools available in their specific lab or company, creating a barrier to cross-disciplinary innovation.
In the real world, the selection of a therapeutic modality like an antibody or peptide is often driven by a company's existing expertise and technology platform rather than a purely agnostic approach to finding the single best tool for a clinical problem. Organizations default to the tools in their toolbox.
The industry's focus on antibodies, which are easy to generate, may be a case of technology dictating the science. Dr. Radvanyi argues that natural ligand-receptor interactions, which often rely on lower affinity and higher avidity, could offer a more nuanced and effective way to modulate immune pathways than high-affinity agonist antibodies.
A key barrier to complex peptide-antibody drugs is manufacturing (CMC). Current methods require separate synthesis and conjugation steps. A fully genetically encoded system—where the entire hybrid molecule is produced in a single cell line—would dramatically lower the barrier to entry and simplify manufacturing, unlocking new drug designs.
The debate isn't about peptides replacing antibodies but about combining them. The future lies in hybrid therapeutics, such as grafting peptides into antibody CDRs or creating fusions that use a peptide for optimal target binding and an antibody scaffold for effector functions, half-life extension, and stability.
While the FDA is often blamed for high trial costs, a major culprit is the consolidated Clinical Research Organization (CRO) market. These entrenched players lack incentives to adopt modern, cost-saving technologies, creating a structural bottleneck that prevents regulatory modernization from translating into cheaper and faster trials.
Scientists in specialized roles like immunogenicity risk becoming siloed service providers. To maintain impact and growth, they must proactively collaborate with other functions like CMC, safety, and quality. This provides a holistic view of drug development and integrates their expertise into the entire process.
The dominance of peptides for GLP-1 therapeutics isn't a failure of antibodies but a success for picking the right tool. Peptides have a natural advantage when the therapeutic strategy involves engineering a natural ligand, making them a better starting point for certain targets like GPCRs.
The long history of now-commonplace technologies like monoclonal antibodies serves as a crucial reminder for the biotech industry. What appears to be an overnight success is often the culmination of decades of hard, incremental scientific work, highlighting the necessity of patience and long-term perspective.
Many innovative drug designs fail because they are difficult to manufacture. LabGenius's ML platform avoids this by simultaneously optimizing for both biological function (e.g., potency) and "developability." This allows them to explore unconventional molecular designs without hitting a production wall later.
With clinical development cycles lasting 7-10 years, junior team members rarely see a project to completion. Their career incentive becomes pushing a drug to the next stage to demonstrate progress, rather than ensuring its ultimate success. This pathology leads to deferred problems and siloed knowledge.