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.
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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.
Competitive advantage in the weight-loss drug market is shifting from maximizing total weight lost to the *quality* of that loss. The next frontier involves preserving muscle while reducing fat and minimizing side effects like nausea. This signals a market evolution toward more nuanced, patient-centric solutions beyond a single metric.
The GLP-1 drug revolution is moving beyond weekly injections for wealthy markets. Upcoming pill-form versions will eliminate the need for refrigerated supply chains, opening up distribution in developing countries. Combined with expiring patents, this focus on form factor and cost will enable mass global adoption.
The emerging Amylin class of obesity drugs shows a consistently more favorable side effect profile than GLP-1 agonists. While weight loss efficacy may be comparable, the superior tolerability positions Amylin as a strong future competitor, either as a standalone option for sensitive patients or as a backbone for combination therapies.
The obesity drug market is moving past the "weight loss Olympics." While high efficacy is the entry ticket, new differentiators are emerging. Companies like Wave Life Sciences are focusing on muscle-sparing properties, while Structure is advancing oral GLP-1s. This indicates a maturing market where patient convenience, quality of weight loss, and long-term maintenance are becoming key value drivers.
Tirzepatide is a rare "once in a blue moon" drug because it is both more potent and better tolerated than its main competitor. This paradoxical profile—achieving superior efficacy with fewer side effects—has established it as the "king of the hill" in the obesity market and created an extremely high bar for any challenger.
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 FDA defines a peptide as an amino acid chain of 40 or less. Blockbuster drugs like Ozempic and Mounjaro are all exactly 39 amino acids long. This perfect fit suggests potential regulatory shaping or clever drug design to fit an advantageous classification.
Lilly's next-generation "triple G" drug, Retratrutide, is not designed to replace its blockbuster Tirzepatide. Due to its "ultra potent" nature and less favorable side effect profile, it will be strategically positioned for a specific subset of patients with very high BMIs (e.g., 40+) who require maximum weight loss.
Wave Life Sciences' drug candidate reduced fat while increasing lean mass, even though total body weight didn't decrease. This signals a strategic shift in obesity treatment, moving beyond simple weight reduction to focus on improving body composition and mitigating muscle loss, a key side effect of GLP-1s.
