CRISPR biotech Intellia plummets as trial paused for safety

Gene-editing specialist Intellia Therapeutics lost more than 45% of its value in pre-market trading today as it revealed phase 3 trials of one of its two priority programmes had been suspended due to safety concerns.

Dosing in the international MAGNITUDE and MAGNITUDE-2 studies of nexiguran ziclumeran (nex-z) in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN), respectively, has been paused while Intellia investigates liver-related side effects leading to hospitalisation of one patient.

The individual is "being closely monitored and is receiving medical intervention," according to the company, which said it is looking into risk-mitigation strategies in consultation with experts and regulators.

Nex-z is one of two late-stage projects on the go at Intellia, a specialist in CRISPR gene-editing co-founded by Nobel Prize winner Jennifer Doudna, along with hereditary angioedema (HAE) candidate NTLA-2002, which completed enrolment in the phase 3 HAELO trial in September.

In January, the company slashed its workforce by more than a quarter and shelved all its other R&D programmes in order to focus on the two programmes, saying they had "the greatest opportunity to create significant, near-term value." It has predicted that its first commercial product launch will take place in 2027, and has been building a commercial operation in anticipation.

The hospitalised patient, who was enrolled in the MAGNITUDE trial, had a grade 4 increase in liver transaminase enzymes – indicating a life-threatening level of liver injury that can be a sign of acute liver failure – as well as increased levels of total bilirubin, another biomarker for liver damage.

"In line with our commitment to patient safety, we have taken immediate action to temporarily pause enrolment in MAGNITUDE and MAGNITUDE-2 as we investigate this recent event," said Intellia president and chief executive John Leonard in a statement issued ahead of a conference call to discuss the development with investors and analysts.

The company said that, at last count, 650 patients with ATTR-CM had been enrolled in MAGNITUDE, and 47 patients with ATTR-PN had been enrolled in MAGNITUDE-2, of whom around 450 have already received a dose of nex-z.

The one-shot therapy, given as an intravenous infusion, is designed to inactivate the TTR gene that encodes for the transthyretin protein, which in ATTR becomes unstable and forms amyloid fibril deposits.

Intellia ended the second quarter of this year with cash reserves of around $630 million, down from $862 million at the end of 2024.