Intellia Therapeutics (NTLA) Study Update summary

Study background, design, and objectives

• NTLA-2002 is a CRISPR-Cas9-based in vivo gene editing therapy for hereditary angioedema (HAE), delivered as a one-time intravenous infusion targeting the KLKB1 gene in the liver.

• The Phase 1/2 study was open-label, single ascending dose (25, 50, 75 mg), with 10 adult patients with Type 1 or 2 HAE; Phase 2 is fully enrolled and randomized.

• Primary objectives included safety, tolerability, and clinical efficacy (attack rate and kallikrein reduction).

• Patients had a mean historical monthly attack rate of 4.6 prior to treatment, with 60% female and 90% on prior long-term prophylaxis.

• Median follow-up was 20.1 months as of February 2024, with ongoing long-term follow-up.

Efficacy and biomarker outcomes

• NTLA-2002 led to dose-dependent, durable reductions in plasma kallikrein: 60% (25 mg), 88% (50 mg), 95% (75 mg).

• Mean monthly HAE attack rate was reduced by 98% over 20 months, with eight of ten patients attack-free after the primary observation period.

• All patients discontinued prophylaxis and remained free of chronic prophylaxis after NTLA-2002.

• The two patients with the highest baseline attack rates became attack-free and maintained this status for up to 23.5 months.

• Mean reduction in moderate to severe attacks was 99% after a single dose.

Safety and tolerability

• NTLA-2002 was well-tolerated at all dose levels, with most adverse events being mild, transient, and primarily infusion-related reactions or fatigue.

• No dose-limiting toxicities, serious adverse events, or Grade 3 or higher adverse events were observed.

• No clinically significant laboratory abnormalities, liver enzyme, platelet, or coagulation changes were reported.

• No correlation was found between body weight and efficacy, supporting flat dosing.

• Patients may enroll in a follow-up study for long-term safety and efficacy monitoring.