The company positions its peptide platform as the ideal middle ground in drug development. They aim to create medicines that are functionally like highly selective, less toxic large biologics (e.g., antibodies) but are structurally designed for the convenience of an oral pill, combining the best attributes of both major drug classes.
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To tackle the high-risk, high-reward obesity market, the company is developing both an injectable and an oral version of the same triple-agonist molecule. The injectable version will enter the clinic first, allowing them to quickly obtain human proof-of-concept and validate the molecule's efficacy before investing heavily in the more complex oral formulation.
Developing a second oral peptide isn't a simple 'copy-and-paste' of the first. The team uses the analogy of having a second child: while past experience makes them faster and more efficient, each new molecule presents its own unique challenges that must be solved from scratch. This highlights the nuanced reality of platform technology leverage.
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.
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.
Protagonist believes its oral IL-23 blocker will not just compete with existing injectables but will capture a new market. They target the over 50% of eligible patients who currently take no therapy due to a dislike of injections or the safety profiles of other oral options, thereby expanding the total addressable market.
The company's strategy for its IL-23 inhibitor isn't just a single drug approval. They follow an established industry model where one successful drug becomes a pipeline for multiple related inflammatory indications like psoriasis, Crohn's, and ulcerative colitis, dramatically expanding its market potential over time.
Acknowledging its late entry into the crowded obesity market, Protagonist consulted key opinion leaders to define the ideal drug profile: an oral "triple G" agonist. By using its peptide platform to build exactly what experts requested, the company aims to leapfrog competitors with a best-in-class product rather than an incremental improvement.
Beyond converting patients from existing injectable therapies, the company's core growth strategy for its oral IL-23 drug is to capture the 50%+ of eligible patients who currently refuse treatment altogether because they dislike injections. This transforms the strategy from market share capture to market creation.
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.
