An elderly patient treated with Intellia Therapeutics’ in vivo CRISPR candidate nexiguran ziclumeran (nex‑z) died after developing severe liver injury, the company disclosed. Intellia halted dosing and screening in the Phase III MAGNITUDE program and notified the FDA, which placed the INDs for both MAGNITUDE trials on clinical hold. Intellia is collaborating with investigators and external experts to investigate Grade 4 transaminase elevations and elevated bilirubin observed in the program; the firm has instituted enhanced early post‑dose lab monitoring at sites. Nex‑z is an LNP‑delivered base‑editing/CRISPR inactivation therapy partnered with Regeneron and designed to permanently reduce TTR production for transthyretin amyloidosis with cardiomyopathy (ATTR‑CM). Intellia reported the initial serious liver event in late October and then confirmed the patient’s death in early November as investigation continued; the company emphasized that the event occurred in a patient with complicating comorbidities and that Grade 4 liver enzyme elevations have been rare across >650 treated patients to date. The safety signal has hit investor confidence—Intellia shares have plunged since the initial hospitalization—and prompted regulatory scrutiny that will shape both the MAGNITUDE readouts and the broader in vivo gene‑editing field. Intellia says it will seek to define risk‑mitigation strategies and exclusion criteria, coordinate with the FDA on required actions, and update the clinical community as more details emerge.