Novartis reported a Phase 3 setback for delpacibart etedesiran (del-desiran), its antibody-oligonucleotide conjugate targeting myotonic dystrophy type 1 (DM1), missing primary endpoints in the HARBOR trial. Novartis said it continues evaluating the full dataset while determining the appropriate path forward. The DM1 miss follows other high-profile issues at Novartis earlier in the year, including the market’s reaction to prior cardiovascular development failures tied to pelacarsen and broader scrutiny around cardiovascular outcomes trials (CVOTs). The overlapping failures raise the stakes for the company’s next DMPK and DMPK-readout strategy as investors weigh translational uncertainty. For the industry, the sequence highlights how costly late-stage timeline risk can cascade across modalities and therapeutic areas, particularly when platform mechanisms depend on tightly linked biology and clinical endpoints. Developers of AOC and nucleic-acid payloads are likely to watch for any program design changes and for additional confirmation of patient stratification and target engagement assumptions.