Madrigal Pharmaceuticals Demonstrates Why Mature Biotech Beats Speculative Bets: A Nektar Reality Check

The Clinical Promise Isn’t Enough

Nektar Therapeutics (NASDAQ: NKTR) achieved impressive momentum in 2025, with its share price climbing on the back of positive phase 2b trial results for rezpegaldesleukin. The immunology space is undoubtedly one of the largest therapeutic markets, and if the drug advances successfully through late-stage studies, the upside could be substantial.

Yet therein lies the fundamental problem: “could” and “if” are the operative words. Nektar remains entirely pre-commercial, with no approved products generating revenue and a balance sheet marked by consistent net losses. This is the textbook risk profile of early-stage biotech development.

When Mid-Stage Success Doesn’t Guarantee Market Success

The biotech graveyard is filled with companies that posted strong intermediate data only to stumble catastrophically in phase 3 trials. aTyr Pharmaceuticals provides a cautionary tale—it generated encouraging mid-stage results before its lead candidate failed advanced testing in September, sending shares into freefall with little prospect of recovery.

For Nektar Therapeutics, rezpegaldesleukin faces another hurdle: it’s targeting immunology territory already dominated by blockbuster competitors like Dupixent and Rinvoq. Even if the drug proves effective against eczema, penetrating a saturated market segment carries execution risk that extends far beyond the laboratory.

The mathematical reality is stark: a phase 3 failure could render the company financially distressed or irrelevant almost overnight.

The Madrigal Pharmaceuticals Playbook: De-Risking Through Commercialization

Madrigal Pharmaceuticals (NASDAQ: MDGL) walked a similar path not long ago—a pre-commercial biotech betting everything on a single clinical candidate. The critical difference: it cleared the finish line.

Rezdiffra, approved in 2024 as the first U.S. treatment for metabolic dysfunction-associated steatohepatitis (MASH), represents a fundamentally different risk profile than Nektar Therapeutics’ pipeline assets. The drug isn’t hypothetical anymore; it’s generating real revenue in a market with genuine unmet needs.

The numbers speak for themselves. In Q3, Rezdiffra delivered $287.3 million in net sales. Trajectory analysis suggests the drug is on course to achieve blockbuster status (defined as $1 billion-plus annual revenue) by 2026. With millions of potential MASH patients across the U.S. and minimal competitive pressure currently, Madrigal operates in an environment where market validation is already underway.

The Approval Landscape Favors Established Demand

Rezdiffra faces one notable requirement: it maintains accelerated approval status, meaning confirmatory trials must eventually demonstrate sustained efficacy. However, this caveat is significantly less ominous than it might initially appear.

The prescription trends and demand metrics already in evidence strongly suggest real-world effectiveness. Regulators, recognizing MASH as an area with substantial unmet medical need, will likely approach confirmatory requirements with the pragmatism the indication warrants. Compare this to the regulatory scrutiny that rezpegaldesleukin would face entering an already-saturated eczema market—the bar is fundamentally different.

Madrigal carries risk, certainly. But it’s the risk of a company with approved product-market fit, not the existential risk of a phase 3 failure or market rejection that haunts Nektar Therapeutics.

The Verdict: Execution Over Speculation

For investors evaluating biotech exposure, the choice between a speculative clinical-stage company and one with commercialization validation is increasingly clear. Nektar Therapeutics offers lottery-ticket upside paired with substantial downside risk. Madrigal Pharmaceuticals offers a more measured risk-reward profile anchored to observable business momentum.

That shift in risk positioning may be the most important distinction investors should consider before making allocation decisions.