Breakthrough drugs aren't always driven by novel biological targets. Major successes like Humira or GLP-1s often succeeded through a superior modality (a humanized antibody) or a contrarian bet on a market (obesity). This shows that business and technical execution can be more critical than being the first to discover a biological mechanism.

In a crowded market like atopic dermatitis, a safe oral drug can carve out a significant niche. Corvus's soquolitinib is positioned to compete against the injectable standard of care (Dupixent) and existing oral JAK inhibitors, which carry black box warnings. This 'safe oral' profile meets a major unmet need for both doctors and patients.

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.

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.

Arcus's strategy isn't to find novel targets, but to leverage its small-molecule expertise on validated targets that are difficult to drug. This de-risks the biology and creates a competitive moat based on technical execution, allowing them to develop a clearly better molecule against incumbents like Merck.

The company's R&D strategy pragmatically filters for targets that are not only highly validated and accessible with its current technology, but are also already on the radar of potential big pharma partners ("strategics"), indicating a clear market and potential exit path.

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.

Macrocyclic peptides are large enough to disrupt difficult protein-protein interactions (like biologics) but small enough to be orally bioavailable (like small molecules). This new modality can tackle targets previously undruggable by conventional small molecules, creating a best-of-both-worlds therapeutic.

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.