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Re: DewDiligence post# 257271

Monday, 03/23/2026 3:10:24 PM

Monday, March 23, 2026 3:10:24 PM

Post# of 257442
According to Claude:

Here's what actually happened:
The main adverse event was the CagriSema disappointment. Novo Nordisk's REDEFINE-1 phase 3 trial results came in below expectations — CagriSema produced 22.7% weight loss at 68 weeks, falling short of the anticipated 25%+, which crashed Novo's stock. A second trial in early 2025 among patients with type 2 diabetes showed only 15.7% weight loss for CagriSema, deepening the disappointment.
This mattered for the whole DACRA class because cagrilintide — the DACRA component in CagriSema — was the most advanced and highest-profile DACRA in clinical development. When that combination failed to impress, it cooled investor and media enthusiasm for the entire mechanism.
Cagrilintide monotherapy (without semaglutide) also underperformed Wegovy as a standalone weight-loss agent.
The rest of the pipeline is earlier-stage and hasn't generated much news: petrelintide (from Roche/Zealand Pharma) is in phase 2 trials, and Structure Therapeutics only initiated its first-in-human phase 1 study for its oral DACRA ACCG-2671 in December 2025. Structuretx
So the quiet isn't mysterious — the leading program underdelivered on its most anticipated clinical readout, and everything else is too early-stage to generate significant news.

and lly?

12:07 PMSearched the webSearched the webLilly's history with DACRAs is actually a long story of repeated exits:
They first cut a phase 2 DACRA (DACRA-042, acquired from KeyBioscience in 2017) from their pipeline back in early 2019. American Physiological Society
They then re-engaged — extending their collaboration with KeyBioscience, with a new molecule planned for a 600-person phase 2 study targeting obesity and osteoarthritis. Nature
Then came the final exit: in February 2025, Lilly removed DACRA QW II (LY3541105) from its phase 1 pipeline. The GLP-1 candidate (tirzepatide) had simply emerged as the more promising program, leaving the DACRA behind. ACS Publications
So Lilly cut DACRAs, came back, then cut them again — which is a pretty clear signal about where they stand on the mechanism relative to their existing assets.

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