Intellia Therapeutics Announces Positive Longer-Term Phase 1 Data for Nexiguran Ziclumeran (nex-z) in Patients with Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy
Intellia Therapeutics (NASDAQ:NTLA) has reported promising long-term Phase 1 data for nexiguran ziclumeran (nex-z) in treating hereditary ATTR amyloidosis with polyneuropathy. The single-dose treatment demonstrated sustained TTR reductions of at least 90% through three years, with significant clinical improvements.
Key findings include: 92% mean serum TTR reduction at 24 months in patients receiving ≥0.3 mg/kg doses (n=33), and 90% reduction at 36 months (n=12). Among 18 patients evaluated at 24 months, 72% showed clinically meaningful improvements in mNIS+7 scores. The treatment was generally well-tolerated, with only mild to moderate infusion-related reactions reported.
The company's Phase 3 MAGNITUDE-2 trial is progressing rapidly, with enrollment completion expected in H1 2026 and a potential BLA submission targeted for 2028.
Intellia Therapeutics (NASDAQ:NTLA) ha riportato dati promettenti a lungo termine (Fase 1) su nexiguran ziclumeran (nex-z) per trattare l’amyloidosi ATTR ereditaria con polineuropatia. Il trattamento a dose unica ha mostrato riduzioni del TTR sostenute di almeno il 90% per tre anni, con significativi miglioramenti clinici.
Tra i risultati chiave: riduzione media del TTR nel siero del 92% a 24 mesi nei pazienti che hanno ricevuto dosi ≥0,3 mg/kg (n=33), e riduzione del 90% a 36 mesi (n=12). Tra 18 pazienti valutati a 24 mesi, il 72% ha mostrato miglioramenti clinicamente significativi nel punteggio mNIS+7. Il trattamento è stato generalmente ben tollerato, con solo lievi o moderate reazioni da infusioni.
Lo studio di fase 3 MAGNITUDE-2 della società prosegue rapidamente, con il completamento dell'iscrizione previsto nel H1 2026 e una potenziale presentazione della BLA mirata al 2028.
Intellia Therapeutics (NASDAQ:NTLA) ha comunicado datos prometedores a largo plazo de Fase 1 sobre nexiguran ziclumeran (nex-z) para tratar la amiloidosis hereditaria ATTR con polineuropatía. El tratamiento de dosis única mostró reducciones sostenidas de TTR de al menos el 90% durante tres años, con mejoras clínicas significativas.
Entre los hallazgos clave: una reducción media de TTR en suero del 92% a los 24 meses en pacientes que recibieron dosis ≥0,3 mg/kg (n=33), y una reducción del 90% a los 36 meses (n=12). Entre 18 pacientes evaluados a los 24 meses, el 72% mostró mejoras clínica-mente significativas en las puntuaciones mNIS+7. El tratamiento fue generalmente bien tolerado, con solo reacciones de infusión leves o moderadas reportadas.
El ensayo de Fase 3 MAGNITUDE-2 de la empresa progresa rápidamente, con la finalización del reclutamiento prevista para el primer semestre de 2026 y una posible presentación de BLA prevista para 2028.
Intellia Therapeutics (NASDAQ:NTLA)은 상염 ATTR 말초신경병증이 있는 유전성 amyloidosis를 치료하기 위한 nexiguran ziclumeran (nex-z)의 장기 1상 데이터가 유망하다고 보고했습니다. 단일 용량 치료는 3년간 최소 90%의 TTR 감소를 지속했으며 임상적 개선이 나타났습니다.
주요 발견으로는: 24개월 간 혈청 TTR 감소 평균 92%로 ≥0.3 mg/kg 투여된 환자(n=33)에서, 36개월 간 90% 감소(n=12). 24개월에 평가된 18명의 환자 중 72%가 mNIS+7 점수에서 임상적으로 의미 있는 개선을 보였습니다. 치료는 일반적으로 잘 견뎌졌으며, 경미~중등도의 주입 관련 반응만 보고되었습니다.
회사의 3상 MAGNITUDE-2 임상은 빠르게 진행 중이며, 2026년 상반기 내 등록 완료가 예상되며 2028년 BLA 제출이 목표로 제시되었습니다.
Intellia Therapeutics (NASDAQ:NTLA) a communiqué des données prometteuses à long terme de la phase 1 pour le nexiguran ziclumeran (nex-z) dans le traitement de l’amylose héréditaire ATTR avec polyneuropathie. Le traitement une seule dose a démontré des réductions TTR soutenues d’au moins 90% sur trois ans, avec des améliorations cliniques significatives.
Les résultats clés incluent: une réduction moyenne du TTR sérique de 92% à 24 mois chez les patients ayant reçu des doses ≥0,3 mg/kg (n=33), et une réduction de 90% à 36 mois (n=12). Parmi 18 patients évalués à 24 mois, 72% ont montré des améliorations cliniquement significatives dans les scores mNIS+7. Le traitement a été généralement bien toléré, avec seulement des réactions infusionales légères à modérées signalées.
L’essai de phase 3 MAGNITUDE-2 progresse rapidement, l’inscription étant attendue au premier semestre 2026 et une potentielle demande de BLA envisagée pour 2028.
Intellia Therapeutics (NASDAQ:NTLA) hat vielversprechende Langzeitdaten der Phase-1-Studie für Nexiguran Ziclumeran (nex-z) zur Behandlung hereditärer ATTR-Amyloidosen mit Polyneuropathie gemeldet. Die Einzeldosenbehandlung zeigte anhaltende TTR-Reduktionen von mindestens 90% über drei Jahre mit signifikanten klinischen Verbesserungen.
Schlüsselbefunde umfassen: 92% mittlere TTR-Senkung im Serum nach 24 Monaten bei Patienten, die ≥0,3 mg/kg erhielten (n=33), und 90%-Reduktion nach 36 Monaten (n=12). Unter 18 Patienten, die nach 24 Monaten bewertet wurden, zeigte 72% klinisch bedeutsame Verbesserungen des mNIS+7-Scores. Die Behandlung wurde im Allgemeinen gut vertragen, mit nur leichten bis mäßigen infusionbedingten Reaktionen.
Die Phase-3-MAGNITUDE-2-Studie schreitet rasch voran, die Rekrutierung soll im ersten Halbjahr 2026 abgeschlossen sein, und eine potenzielle BLA-Einreichung für 2028 wird angestrebt.
Intellia Therapeutics (NASDAQ:NTLA) قد أبلغت عن بيانات واعدة طويلة الأجل من المرحلة الأولى عن nexiguran ziclumeran (nex-z) في علاج اعتلالات ATTR الوراثية مع اعتلال محيطي. أظهر العلاج بجرعة واحدة خفضاً مستداماً لـ TTR بنسبة لا تقل عن 90% على مدى ثلاث سنوات، مع تحسنات سريرية كبيرة.
تشمل النتائج الرئيسية: خفض متوسط TTR في المصل بنسبة 92% عند 24 شهراً في المرضى الذين تلقوا جرعات ≥0.3 mg/kg (ن=33)، وخفضاً بنسبة 90% عند 36 شهراً (ن=12). من بين 18 مريضاً قيموا عند 24 شهراً، أظهر 72% تحسنات سريرية ذات معنى في درجات mNIS+7. كان العلاج بشكل عام متحملاً جيداً، مع تقارير عن تفاعلات مرتبطة بالحقن خفيفة إلى متوسطة.
تتقدم تجربة MAGNITUDE-2 في المرحلة 3 بسرعة، مع إتمام التسجيل المتوقع في النصف الأول من 2026 واحتمال تقديم طلب BLA مستهدف في 2028.
Intellia Therapeutics (NASDAQ:NTLA) 已报道关于 nexiguran ziclumeran（nex-z）在治疗遗传性 ATTR淀积性神经病变方面的长期一期数据，显示出希望。单剂量治疗显示 三年内 TTR 至少降低90%，并伴有显著的临床改善。
关键发现包括：在接受≥0.3 mg/kg剂量的患者（n=33）中，24 个月血清 TTR 平均下降92%，以及在36个月时下降90%（n=12）。在24个月评估的18名患者中，72%在mNIS+7评分上显示出临床上有意义的改善。治疗总体耐受良好，报道的静脉给药相关反应多为轻至中度。
该公司的3期 MAGNITUDE-2 研究进展迅速，2026年上半年预计完成入组，且可能在＜b＞2028年提交 BLA。
- Sustained TTR reductions of 90-92% maintained through three years with single dose
- 72% of evaluated patients showed clinically meaningful improvements in mNIS+7 scores
- 89% of patients showed improvement or stability in PND scores through 24 months
- Generally favorable safety profile with only mild/moderate infusion reactions
- Phase 3 MAGNITUDE-2 trial advancing rapidly toward H1 2026 enrollment completion
- Three participants experienced Grade >3 liver enzyme elevations
- BLA submission timeline extends to 2028, indicating a lengthy approval process
- Limited patient sample size in long-term data (only 12 patients at 36 months)
Insights
Intellia's one-time gene editing therapy shows impressive 90%+ TTR reduction maintained for 3 years with clinical improvements in ATTR-PN patients.
Intellia's CRISPR therapy nexiguran ziclumeran (nex-z) is demonstrating remarkable durability with a single dose maintaining over
The
Most impressive are the clinical outcomes: 72% of patients showed clinically meaningful improvements in mNIS+7 scores (≥4 points) at 24 months - including patients who had previously progressed on patisiran, suggesting nex-z may benefit patients who fail current therapies. The
The consistent safety profile, with primarily mild infusion reactions and no new drug-related events in the follow-up period, is encouraging for a gene editing approach. The three cases of elevated liver enzymes resolved spontaneously, suggesting manageable hepatic effects.
The accelerating Phase 3 MAGNITUDE-2 trial timeline, with projected enrollment completion in H1 2026 and potential BLA filing by 2028, positions Intellia to potentially deliver the first in vivo CRISPR therapy for a progressive genetic disease. If approved, nex-z would represent a one-time treatment option competing with chronic therapies like patisiran (Onpattro) and inotersen (Tegsedi) in the ATTR-PN market.
- One dose of nex-z led to rapid, deep and durable TTR reductions, with mean reductions of at least
90% from baseline sustained through three years - Stabilization or improvement in disease-related clinical measures observed at 24 months
- Continue to observe generally favorable safety data with no new drug-related events within the follow-up period
- Data presented today at the 5th International ATTR Amyloidosis Annual Meeting for Patients and Doctors with simultaneous publication in the New England Journal of Medicine
- Expect to complete enrollment in multi-national Phase 3 MAGNITUDE-2 trial in first half 2026 to support a potential BLA filing by 2028
CAMBRIDGE, Mass., Sept. 25, 2025 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today announced longer-term follow-up data from the ongoing Phase 1 study of investigational nexiguran ziclumeran (nex-z) for the treatment of hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). Results were presented in an oral session on Thursday, September 25 at the 5th International ATTR Amyloidosis Annual Meeting for Patients and Doctors in Baveno, Italy. The results were simultaneously published in the New England Journal of Medicine, and the presentation will be available on the Scientific Publications & Presentations section of intelliatx.com.
"After receiving a one-time treatment of nex-z, patients continue to experience durable TTR reductions, including those who have reached three years of follow-up,” said Intellia President and Chief Executive Officer John Leonard, M.D. “The results from our ongoing Phase 1 study of nex-z support our belief that deeper and more consistent reductions in TTR translate to better outcomes for patients. Our Phase 3 MAGNITUDE-2 study is progressing swiftly, and we are eagerly anticipating the results, which we believe will demonstrate nex-z’s potential to halt or reverse disease progression in people living with ATTRv-PN.”
Continuation of Deep and Durable Serum TTR Reduction
Deep, durable and consistent TTR reductions continue to be observed. Across patients who received a one-time dose of 0.3 mg/kg or higher (n=33), the mean serum TTR reduction at 24 months was
Evidence of Stability or Improvement on Clinical and Biomarker Measures
Favorable trends indicating stability or improvement were observed in most patients with ATTRv-PN after a single dose of nex-z. Stability or improvement was based on evaluation of multiple clinical and biomarker measures, including Neuropathy Impairment Score (NIS), modified Neuropathy Impairment Score +7 (mNIS+7), modified body mass index (mBMI), Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) questionnaire, neurofilament light chain (NfL), and polyneuropathy disability (PND) score.
Among the 18 patients in whom a 24-month mNIS+7 assessment was completed by the data cutoff date (April 11, 2025), 13 (
Safety Summary
Nex-z has been generally well tolerated as of the data cutoff date across all patients and at all dose levels tested. The most commonly reported treatment-related adverse events were infusion-related reactions, which were mild or moderate and did not result in any discontinuations. As previously reported, three participants had Grade >3 liver enzyme elevations that were not considered serious, were asymptomatic and resolved spontaneously without medical intervention or sequelae.
Phase 3 MAGNITUDE-2 Trial Advancing Rapidly
Intellia began dosing patients in the Phase 3 MAGNITUDE-2 trial in April 2025. Patient screening is advancing rapidly, and enrollment completion is expected in the first half of 2026. Intellia anticipates submitting a biologics license application (BLA) for ATTRv-PN by 2028. MAGNITUDE-2 is a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of nexiguran ziclumeran (nex-z) in approximately 50 patients with hereditary transthyretin ATTR amyloidosis with polyneuropathy (ATTRv-PN). The primary endpoints of the study are a change in modified neuropathy impairment score and a change in serum TTR levels. Adult patients with ATTRv-PN are randomized 1:1 to receive a single 55 mg infusion of nex-z or placebo. For more information on MAGNITUDE-2 (NCT06672237), please visit clinicaltrials.gov.
About the Nexiguran Ziclumeran (nex-z) Phase 1 Clinical Trial
The global Phase 1 trial is an ongoing open-label, multi-center, two-part study of nex-z in adults with hereditary transthyretin ATTR amyloidosis with polyneuropathy (ATTRv-PN) or transthyretin ATTR amyloidosis with cardiomyopathy (ATTR-CM). Part 1 of the ATTRv-PN arm of the study is an open-label, single-ascending dose escalation cohort and Part 2 is an open-label, single-dose expansion cohort. Visit clinicaltrials.gov (NCT04601051) for more details.
About Nex-z
Based on Nobel Prize-winning CRISPR/Cas9 gene editing technology, nex-z has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis. Nex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein. Interim Phase 1 clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development and commercialization collaboration with Regeneron Pharmaceuticals, Inc.
About Transthyretin (ATTR) Amyloidosis
Transthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive and fatal disease. Hereditary ATTR (ATTRv) amyloidosis occurs when a person is born with mutations in the TTR gene, which causes the liver to produce structurally abnormal transthyretin (TTR) protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system. ATTRv amyloidosis predominantly manifests as polyneuropathy (ATTRv-PN), which can lead to nerve damage, or cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some individuals without the genetic mutation produce non-mutated, or wild-type TTR proteins that become unstable over time, misfolding and aggregating in disease-causing amyloid deposits. This condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily affects the heart. There are an estimated 50,000 people worldwide living with ATTRv amyloidosis and between 200,000 and 500,000 people with ATTRwt amyloidosis. There is no known cure for ATTR amyloidosis and currently available medications are limited to slowing accumulation of misfolded TTR protein.
About Intellia Therapeutics
Intellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. Since its inception, Intellia has focused on leveraging gene editing technology to develop novel, first-in-class medicines that address important unmet medical needs and advance the treatment paradigm for patients. Intellia’s deep scientific, technical and clinical development experience, along with its people, is helping set the standard for a new class of medicine. To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies. Learn more at intelliatx.com and follow us @intelliatx.
Forward-Looking Statements
This press release contains “forward-looking statements” of Intellia Therapeutics, Inc. (“Intellia” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellia’s beliefs and expectations regarding: the safety, tolerability, efficacy, success and advancement of its clinical programs for nexiguran ziclumeran or “nex-z” (also known as NTLA-2001) for transthyretin (“ATTR”) amyloidosis, including the ability to successfully complete its global Phase 3 MAGNITUDE-2 study for hereditary transthyretin ATTR amyloidosis with polyneuropathy (“ATTRv-PN”) pursuant to its clinical trial applications and investigational new drug submissions; its expectation to complete enrollment in the MAGNITUDE-2 trial in the first half of 2026; its belief that a single dose of nex-z leads to deep, durable and consistent reductions in serum TTR and that increasingly deep reductions in TTR levels translate to better outcomes for patients; its belief that the MAGNITUDE-2 trial will demonstrate nex-z’s potential to halt or reverse disease progression in people living with ATTRv-PN; and its expectation to submit a biologics license application for nex-z for the treatment of ATTRv-PN by 2028.
Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellia’s ability to protect and maintain its intellectual property position; risks related to valid third party intellectual property; risks related to Intellia’s relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to regulatory agencies’ evaluation of regulatory filings and other information related to our product candidates, including nex-z; uncertainties related to the authorization, initiation and conduct of studies and other development requirements for our product candidates, including uncertainties related to regulatory approvals to conduct clinical trials; the risk that any one or more of Intellia’s product candidates, including nex-z, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies for the same product candidate or Intellia’s other product candidates; and risks related to Intellia’s reliance on collaborations, including that its collaboration with Regeneron Pharmaceuticals, Inc. will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellia’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Intellia’s most recent annual report on Form 10-K and quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law.
Intellia Contacts:
Investors:
Jason Fredette
Vice President, Investor Relations and Corporate Communications
jason.fredette@intelliatx.com
Media:
Matt Crenson
Ten Bridge Communications
media@intelliatx.com
mcrenson@tenbridgecommunications.com
FAQ
What are the latest Phase 1 results for Intellia's (NTLA) nexiguran ziclumeran in ATTR amyloidosis?
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