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 GLP-1 has been a known target for a long time, the recent explosion in peptide therapeutics was primarily enabled by solving the historical challenge of poor half-life and exposure. Achieving one- or two-week half-lives through techniques like fatty acid acylation was the critical technological unlock for the field.

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.

Unlike traditional small molecules that need a pocket on a target protein, molecular glues work by changing the surface of an E3 ligase. This modified surface then perfectly matches and binds the target protein, enabling its degradation without requiring a direct drug-to-target binding site.

Despite its current widespread use, experts predict that the traditional method of cysteine engineering for ADC linkers will be phased out. Newer, more precise approaches like enzymatic conjugation and non-canonical amino acids offer superior control over payload attachment and stability, signaling an industry-wide shift toward more advanced and reliable bioconjugation strategies.

An AI model analyzing drug delivery peptides discovered that adding a flexible amino acid before the active end group significantly improved cell entry. This was not a commonplace understanding in the field. Initially questioned by chemists, the insight was experimentally validated, showing how AI can augment human expertise by revealing novel scientific mechanisms.

Mini-proteins are framed as a superior drug modality that merges the key strengths of traditional therapies. They possess the high selectivity characteristic of biologics like antibodies, while also having the stability and formulation advantages of small-molecule drugs. This combination allows them to precisely target difficult receptors while avoiding common off-target effects or instability issues.

CEO Jonathan Steckbeck simplifies a complex topic by describing peptides as a "Goldilocks modality." They sit between small molecules (good access, poor specificity) and biologics (poor access, good specificity), ideally offering the best of both worlds for targeted drug delivery.

Merck's biocatalysis platform starts with enzymes from nature and uses directed evolution—iterative lab-based mutation and selection—to create novel manufacturing tools. This process rapidly builds unnatural functions, enabling the scalable synthesis of complex drugs that would otherwise be impractical.