Clinical Safety And Efficacy Uncertainty At Higher DosesUnblinded data showing transient decreases in kidney function and temporary albumin increases at higher doses, combined with indications that the initial low dose may be sub‑therapeutic, make higher‑dose results pivotal and increase clinical risk.
Preclinical Safety Signal ConcernsPreclinical infusion‑related effects in mice, including drops in body temperature and blood pressure, raise potential readthrough risks for related programs and heighten regulatory scrutiny.
Regulatory Uncertainty From Partial Clinical HoldA partial clinical hold placed by the FDA based on preclinical concerns creates regulatory uncertainty and prevents U.S. patient enrollment, complicating the development pathway.