Intellia Releases Promising Two-Year Data for Nex-Z in ATTR Amyloidosis
Intellia Therapeutics has unveiled encouraging two-year follow-up data from its Phase 1 trial of nexiguran ziclumeran (nex-z), a treatment for hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). These findings indicate significant mean reductions in serum transthyretin (TTR) levels, achieving a 90% decrease by Day 28, alongside improved clinical and biomarker outcomes over the 24-month period, even in patients who had previously shown progression while using patisiran. Importantly, the safety profile remained favorable, with no new drug-related adverse events reported. The company’s MAGNITUDE-2 Phase 3 trial is currently ongoing, aimed at further evaluating nex-z, with a goal for a biologics license application submission by 2028.
Key Advantages
- Prolonged and consistent TTR reductions maintained for two years post a single nex-z dose, indicating potential long-term efficacy.
- Clinically significant advancements in ATTRv-PN outcomes at 24 months, including improvements in patients previously treated with other therapies.
- Generally favorable safety and tolerability profile, as no new drug-related adverse events were reported, suggesting lower patient risk.
- Positive enrollment trends in the ongoing MAGNITUDE-2 trial highlight strong interest and strengthen potential future data to support regulatory approval.
Potential Challenges
- Risks associated with the MAGNITUDE-2 trial could affect the timeline for submitting a biologics license application by 2028.
- The reliance on forthcoming clinical outcomes to confirm nex-z’s efficacy introduces uncertainty around future developments and market predictions.
- Intellia has recognized risks regarding its intellectual property, including possible challenges with its partnership with Regeneron Pharmaceuticals, which may impede nex-z’s commercialization.
Frequently Asked Questions
What are the main findings from the two-year follow-up of nex-z?
Deep, durable reductions in TTR levels were observed, sustained for two years following a single dose of nex-z.
How does nex-z affect patients previously on patisiran?
Nex-z demonstrated clinically meaningful improvements in patients who had previously shown progression on patisiran.
What is the duration of the clinical trial for nex-z?
The Phase 1 trial of nex-z remains active, with results monitored up to two years post-dosing.
What is the MAGNITUDE-2 study?
MAGNITUDE-2 is a critical Phase 3 clinical trial assessing the efficacy of nex-z in participants with ATTRv-PN.
What safety results were observed for nex-z?
Overall, nex-z was well tolerated with only mild or moderate infusion-related reactions noted, and no new adverse events reported.
$NTLA Insider Trading Activity
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$NTLA Hedge Fund Activity
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$NTLA Analyst Ratings
In recent months, Wall Street analysts issued reports on $NTLA, with one firm recommending a buy and no sell ratings reported.
The recent analyst ratings include:
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Full Release
- Deep, durable reductions in TTR were maintained at the two-year mark following a single dose of nex-z.
- Clinically relevant improvements in ATTRv-PN outcomes were observed at 24 months, notably in patients who had progressed on patisiran.
- Continued favorable safety and tolerability observed in the full Phase 1 cohort, with no new drug-related adverse events in the follow-up period.
- Enrollment in MAGNITUDE-2 is progressing well, designed to measure clinical outcomes and support a BLA submission by 2028.
Intellia Reports Positive Phase 1 Results for Nexiguran in ATTRv-PN
(NEWSWIRE) — Intellia Therapeutics, Inc. (NASDAQ:NTLA) has shared encouraging two-year follow-up data from the ongoing Phase 1 trial of its investigational treatment, nexiguran ziclumeran (nex-z). This therapy targets hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). The new findings were presented on May 18 at the 2025 Peripheral Nerve Society (PNS) Annual Meeting in Edinburgh, United Kingdom. Additionally, the design for the Phase 3 MAGNITUDE-2 trial of nex-z in ATTRv-PN was also showcased in a poster session.
“We are pleased to share new findings at PNS, which continue to support our growing body of evidence that a single dose of nex-z leads to deep, durable, and consistent reductions in serum TTRs, with evidence of disease stability or clinically meaningful improvements in neuropathic impairment measures through two years,” stated Intellia President and CEO John Leonard, M.D. “These data are also the first to show improvement in patients who had previously progressed on patisiran, further validating the hypothesis that deeper reductions in TTR levels may correlate with improved outcomes in ATTR amyloidosis.”
ATTRv-PN Trial Results
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Significant Serum TTR Reduction:
Among patients receiving a single dose of 0.3 mg/kg or higher (n=33), the mean serum TTR reduction by Day 28 was 90% (mean absolute serum TTR level: 23.8 µg/mL). These serum levels remained stable for at least 24 months. -
Clinical and Biomarker Evidence of Disease Modification:
Positive trends suggesting stability or improvement were observed in ATTRv-PN patients. This included six individuals with a mean duration of treatment on patisiran of 5.5 years, who previously exhibited disease progression. The stability or improvement was assessed through multiple clinical and biomarker measures, such as the Neuropathy Impairment Score (NIS), modified Neuropathy Impairment Score +7 (mNIS+7), modified BMI (mBMI), Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) questionnaire, and neurofilament light chain (NfL). Among the 18 patients who underwent mNIS+7 assessment at 24 months, 14 demonstrated a clinically significant improvement of ≥4 points as of the April 11, 2025, data cutoff, including 5 of the 6 patients formerly on patisiran. Detailed results are provided in the table below.
| Clinical and Biomarker Measures | Change from Baseline at Month 12 | Change from Baseline at Month 24 |
| Part 1: Dose-escalation portion N=15* | ||
| NIS, mean (SD) | -2.0 (5.3) | -4.5 (7.4) |
| Part 2: Dose expansion portion N=21* | ||
| NIS, mean (SD) | -2.1 (10.2) | -5.2 (10.7) |
| mNIS+7, mean (SD) (overall) | -0.6 (11.1) | -8.5 (9.6) |
| mNIS+7, mean (SD) (patients previously on patisiran)† | -6.3 (11.6) | -6.5 (9.8) |
| Full cohort N=36‡ | ||
| Norfolk QoL-DN, mean (SD)** | -3.5 (21.0) | -8.5 (19.3) |
| NfL (% change from baseline)*** | -8.6 (41.7) | N/A |
| mBMI, mean (SD)** | 13.4 (93.2) | 39.0 (87.1) |
* Data cutoff April 11, 2025; ** Data cutoff August 21, 2024; *** Data cutoff April 12, 2024;
†N=6; ‡ 24-month data in 19 patients; N/A: Data not available at Month 24
Negative changes indicate improvement in NIS, mNIS+7, Norfolk QoL-DN, and NfL metrics, while positive changes reflect improvements in mBMI.
The study is ongoing, and the reported results reflect the available data as of the cutoff date.
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Safety Information:
Additional safety data regarding nex-z is expected as the study progresses.
Intellia’s Nexiguran Ziclumeran Shows Promise in Ongoing Clinical Trials
- The latest data indicates that the treatment has been generally well tolerated among all patients and at every tested dose level. Mild to moderate infusion-related reactions were the most frequently reported treatment-related adverse events, but these did not lead to any discontinuations. Liver enzyme abnormalities observed were asymptomatic, considered non-serious, and resolved spontaneously without medical intervention.
The presentation detailing these findings will be accessible in the Scientific Publications & Presentations section of intelliatx.com.
Overview of the Nexiguran Ziclumeran (nex-z) Clinical Program
The global Phase 1 trial is ongoing and consists of an open-label, multi-center, two-part study of NTLA-2001 in adults diagnosed with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) or transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Part 1 features a single-ascending dose escalation cohort, while Part 2 entails a single-dose expansion cohort.
For more details, refer to clinicaltrials.gov (NCT04601051).
About the MAGNITUDE-2 Study
The pivotal Phase 3 MAGNITUDE-2 clinical trial is designed as a randomized, double-blind, placebo-controlled study aimed at evaluating the efficacy and safety of nexiguran ziclumeran (nex-z). Approximately 50 patients with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN) will participate. The study’s primary endpoints include changes in the modified neuropathy impairment score and serum TTR levels. Participants will be randomized 1:1 to receive a single 55 mg infusion of either nex-z or a placebo.
For additional information on the MAGNITUDE-2 study, visit clinicaltrials.gov (NCT06672237).
Understanding Nexiguran Ziclumeran
Nex-z is based on Nobel Prize-winning CRISPR/Cas9 gene editing technology and aims to become the first one-time treatment for transthyretin (ATTR) amyloidosis. It specifically targets the TTR gene responsible for producing the transthyretin (TTR) protein. Interim Phase 1 clinical data indicates that treatment with nex-z has resulted in significant and prolonged reductions in TTR levels. Intellia leads its development and commercialization in collaboration with Regeneron Pharmaceuticals, Inc.
Insight into Transthyretin (ATTR) Amyloidosis
ATTR amyloidosis is a rare, progressive, and often fatal condition. Hereditary ATTR (ATTRv) amyloidosis occurs due to mutations in the TTR gene, resulting in the production of abnormal TTR proteins that misfold and accumulate as amyloid deposits. This can lead to serious complications affecting the heart, nerves, and digestive system. The condition mainly presents as polyneuropathy (ATTRv-PN) and cardiomyopathy (ATTRv-CM). In addition, some individuals without genetic mutations develop wild-type ATTR (ATTRwt) amyloidosis primarily affecting the heart. Currently, it is estimated that 50,000 people globally live with ATTRv amyloidosis, alongside a range of 200,000 to 500,000 individuals with ATTRwt amyloidosis. Unfortunately, there is no known cure, and existing medications only slow down the accumulation of misfolded proteins.
About Intellia Therapeutics
Intellia Therapeutics, Inc. (NASDAQ: NTLA) is a clinical-stage gene editing company focused on advancing medicine through CRISPR-based therapies. Since its founding, Intellia has worked to harness gene editing technology to create innovative treatments that address critical medical needs. Their expertise spans scientific research, technical development, and clinical trials, positioning them as leaders in a new era of medicine. The company is continually enhancing its CRISPR platform with novel editing and delivery technologies.
Forward-Looking Statements
This press release contains “forward-looking statements” from Intellia Therapeutics, Inc. concerning the future expectations and results of its clinical programs for nexiguran ziclumeran (also known as NTLA-2001) for transthyretin (ATTR) amyloidosis. These statements involve risks and uncertainties, including the company’s ability to complete the Phase 3 MAGNITUDE-2 study and the efficacy of nex-z. Actual outcomes may differ significantly from these projections, influenced by various factors like regulatory challenges and collaboration risks. For a detailed discussion of risks, refer to the “Risk Factors” section in Intellia’s most recent annual report (Form 10-K) and quarterly report (Form 10-Q).
Intellia Contacts:
Investors:
Brittany Chaves
Senior Manager, Investor Relations
[email protected]
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Ten Bridge Communications
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