Upstream Bio shares are crashing despite meeting primary endpoints in their Phase 2 asthma trial, as sophisticated investors identify a critical flaw in the data: a "dose-inversion" where the drug performed worse at the commercially vital extended dosing schedule. Key Drivers: The Data Disconnect: While the 12-week dose showed a competitive 56% reduction in asthma attacks (AAER), the 24-week dose—intended to be the drug's main selling point against competitors—showed a significantly weaker 39% reduction. Commercial Thesis Failure: The bull case relied on UPB offering a "once-every-6-months" injection to beat monthly competitors like Tezspire (Amgen) and Dupixent (Sanofi). With only 39% efficacy at that interval (vs. competitors' ~50%+), the "convenience" advantage is effectively dead. Scientific Red Flag: The "inverted dose response" (where more drug = less effect) creates regulatory uncertainty. The FDA typically requires additional, expensive trials to resolve such discrepancies, delaying any potential approval timeline. Outlook: The stock is repricing from a "potential best-in-class" premium to a "me-too" discount. Unless UPB can prove the 24-week data was a statistical anomaly in Phase 3, the drug lacks a competitive moat in a crowded indications market.
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