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.

Contrary to the popular belief that antibody development is a bespoke craft, modern methods enable a reproducible, systematic engineering process. This allows for predictable creation of antibodies with specific properties, such as matching affinity for human and animal targets, a feat once considered a "flight of fancy."

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.

T-cell receptor (TCR) therapies offer a significant advantage over monoclonal antibodies by targeting intracellular proteins. They recognize peptides presented on the cell surface, effectively unlocking 90% of the proteome and requiring far fewer target molecules (5-10 copies vs. 1000+) to kill a cancer cell.

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.

As biologics evolve into complex multi-specific and hybrid formats, the number of design parameters (valency, linkers, geometry) becomes too vast for experimental testing. AI and computational design are becoming essential not to replace scientists, but to judiciously sample the enormous design space and guide engineering efforts.

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.

Antibodies bind to specific amino acid sequences, making them unable to distinguish between a protein's healthy and toxic structural forms. Alt-Pep's synthetic peptides use a complementary structure (alpha-sheet) to selectively bind only the toxic oligomers, enabling both targeted therapy and highly specific diagnostics.