Jake

Jake asked for more color on the macroeconomic environment, specifically if trends that affected 2025 are abating in 2026, and about the opportunity with medical schools for one-to-one partnerships.

Answer

John Doherty, CFO, expressed more confidence moving forward, noting that while some downward pressure from tariffs remains, deal closures are improving, and the company is managing through previous delays. Joseph DeVivo, Chairman and CEO, anticipates medical schools will be a strong contributor in 2026, particularly in Q2. He highlighted the strong commitment of new medical students to learn ultrasound, their preference for Butterfly, and the long-term brand loyalty this builds as they progress through their careers.

Jake asked if the liver enzyme elevations seen with nex-z are specific to TTR gene editing with no read-through to the rest of the pipeline, delving into the underlying biology and the influence of immune-mediated evidence.

Answer

President and CEO John Leonard stated it's premature to speculate on the molecular events driving the liver injury. He confirmed they see hallmarks of an immunologic process, leading to the proposed use of steroids. He does not believe there's read-through to the rest of the pipeline due to different genes, edits, patient populations, and demographic characteristics, noting no Grade 3 or 4 elevations in HAELO or other studies. He hopes to test the strategies to achieve the attractive efficacy profile.

Jake asked if Intellia's current stance is that liver enzyme elevations from nex-z are specific to TTR gene editing with no read-through to the rest of the pipeline, inquiring about the underlying biology and the influence of immune-mediated evidence on this analysis.

Answer

President and CEO John Leonard stated that Intellia cannot speculate on the molecular events driving the liver enzyme elevations. He confirmed that while the process has hallmarks of an immunologic reaction, it's unclear if TTR editing itself or other factors are responsible. He emphasized that no Grade 3 or 4 elevations have been observed in other pipeline studies like HAELO, suggesting the phenomenon is primarily playing out in the CM patient population and does not speak across the entire pipeline due to different genes, edits, and patient demographics.