NTLA 8-K
Intellia Therapeutics, Inc. (NTLA)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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Item 7.01 Regulation FD Disclosure.
On November 8, 2025, Intellia Therapeutics, Inc. (the “Company”) issued a press release titled “Intellia Therapeutics Presents Positive Pooled Phase 1/2 Data for Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema.” A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
On November 10, 2025, the Company issued a press release titled “Intellia Therapeutics Presents Positive Longer-Term Phase 1 Data for Nexiguran Ziclumeran (nex-z) in Patients with Transthyretin (ATTR) Amyloidosis with Cardiomyopathy.” A copy of the press release is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
The information under this Item 7.01, including Exhibits 99.1 and 99.2 hereto, are being furnished herewith and shall not be deemed “filed” for the purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall such information be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01. Other Events.
Phase 1/2 Data for Lonvoguran Ziclumeran
On November 8, 2025, the Company announced positive new clinical data from the ongoing Phase 1/2 trial of lonvoguran ziclumeran (“lonvo-z,” also known as NTLA-2002) in patients with hereditary angioedema (“HAE”). Lonvo-z is an investigational in vivo CRISPR-based gene editing therapy that is currently in development as a one-time treatment for HAE. The global Phase 1/2 trial is evaluating the safety and efficacy of lonvo-z in adults with Type I or Type II HAE. These results were shared in an oral presentation at the American College of Allergy, Asthma & Immunology 2025 Annual Scientific Meeting in Orlando, Florida on November 8, 2025.
The clinical data presented on November 8 was based on a pooled analysis of all 32 patients who have received a one-time 50 mg treatment of lonvo-z via intravenous infusion in the Phase 1/2 trial. Of the 32 patients, 15 had initially received the 50 mg dose at study day 1 (four in Phase 1 and 11 in Phase 2) and 17 were treated after unblinding of the Phase 2 clinical trial for the primary analysis (11 had originally received a 25 mg dose of lonvo-z, which was determined to be a suboptimal dose, and six had previously received placebo). The data cut-off date for the analysis was August 29, 2025.
Deep, stable and durable reductions in plasma kallikrein were observed in all patients, with a mean reduction of 89% at month 24. Among the 32 patients, 31 (97%) were both attack-free and long-term prophylaxis (“LTP”)-free as of the data cutoff date, with 24 (75%) being attack-free and LTP-free for at least seven months (up to 32 months for patients with the longest follow-up). Of the 11 patients who initially received the 50 mg dose of lonvo-z in Phase 2, 10 were attack-free and LTP-free (nine for 7-32 months and one for <6 months). The one patient who was not attack-free and LTP-free as of the data cutoff date had a 59% reduction from baseline in their monthly attack rate.
After a 50 mg dose, a well-tolerated safety profile was observed in the Phase 1/2 trial for up to three years of follow-up with no long-term risks identified. The most frequent treatment-emergent adverse events (“TEAEs”) within 28 days of infusion were infusion-related reactions, fatigue and headache. The most frequent TEAEs reported ≥28 days after infusion up to long-term follow-up (“LTFU”) were nasopharyngitis, upper respiratory tract infection, back pain, arthralgia and COVID-19. A single Grade 2 AST elevation was reported among all patients in the Phase 1/2 trial who received a 50 mg dose of lonvo-z. This event had an onset at study day 1 and spontaneously resolved by study day 4 in a patient previously treated with lonvo-z 25 mg. Safety of the 50 mg dose after patients received the suboptimal dose (25 mg) was consistent with the overall clinical trial population. There were no clinically significant shifts in liver enzymes or coagulation parameters. One serious adverse event (“SAE”), a pulmonary embolism, was observed in a patient with multiple risk factors one year after the infusion, and the event resolved without sequelae. In LTFU (n=17), there were no SAEs or TEAEs reported with lonvo-z 50 mg, as of the data cutoff date.
A one-time 50 mg treatment of lonvo-z is being further evaluated in patients with HAE in the ongoing global Phase 3 HAELO clinical trial, which completed enrollment in September 2025. The Company expects to report topline data from the HAELO Phase 3 trial by mid-2026.
Phase 1 Data for Nexiguran Ziclumeran
On November 10, 2025, the Company announced positive new clinical data from the ongoing Phase 1 trial of nexiguran ziclumeran (“nex-z,” also known as NTLA-2001) in patients with transthyretin (“ATTR”) amyloidosis with cardiomyopathy (“ATTR-CM”). Nex-z is an investigational in vivo CRISPR-based gene editing therapy in development as a one-time treatment for ATTR
amyloidosis. The Phase 1 clinical trial is an open-label, two-part trial evaluating the safety and efficacy of nex-z in patients with ATTR-CM. These results were shared in a late-breaking oral presentation at the American Heart Association Scientific Sessions 2025 in New Orleans, Louisiana on November 10, 2025.
The Phase 1 trial enrolled 36 patients, a high proportion of whom had advanced disease at baseline (50% classified as New York Heart Association (“NYHA”) Class III and 31% with variant ATTR-CM). The data cut-off date for the clinical data presented on November 10 was August 23, 2025.
Across all patients in the Phase 1 trial, a one-time treatment of nex-z led to consistently rapid, deep and sustained serum TTR reduction, regardless of baseline levels, through the data cut-off date. All patients in the Phase 1 trial continued to show a sustained response with no evidence of a waning effect over time. Among the 9 patients who reached 36 months of follow-up, the mean serum TTR reduction was 87% (mean absolute serum TTR level of 22.9 µg/mL [Mean 95% CI, 16.0 to 29.8]), consistent with the overall cohort at month 24.
Patients dosed with nex-z in the Phase 1 trial continued to show evidence of disease stabilization or improvement at month 24 compared to baseline. Evaluation was based on multiple markers of cardiomyopathy, including N-terminal pro-B-type natriuretic peptide (“NT-proBNP”), high sensitivity Troponin T (“hs-Troponin T”), 6-minute walk test (“6MWT”), Kansas City Cardiomyopathy Questionnaire (“KCCQ”), and echocardiographic measures.
At 24 months, NT-proBNP and hs-Troponin T, which are markers known to be associated with disease progression, showed stability or improvement in 70% and 85% of patients in the Phase 1 trial, respectively. Preservation of functional status, as measured by 6MWT, was observed with 69% of patients either showing stability or improvement. Notably, 81% of patients were stable or improved in their NYHA classification at 24 months, including improvement in 83% of patients with NYHA Class III. There also was evidence of benefit in quality of life, regardless of NYHA Class at baseline as assessed by KCCQ. Assessment of cardiac structure with echocardiography, showed a similar pattern of stability with limited progression of cardiac remodeling at 24 months.
Additionally, findings from a mortality assessment were presented. This post-hoc analysis was conducted on a cohort of 1,792 ATTR-CM patients from the National Amyloidosis Center whose baseline characteristics were matched to those of the Phase 1 nex-z population. The analysis showed patients receiving a one-time treatment with nex-z in the Phase 1 trial had an all-cause mortality rate of 3.9 per 100 patient-years, while the matched cohort had an all-cause mortality rate of 12.7 per 100 patient-years (HR 0.27, p=0.009).
Nex-z was generally well tolerated across all patients in the Phase 1 clinical trial. The most commonly reported treatment-related adverse events were infusion-related reactions and transaminase elevations. In this Phase 1 population, liver enzyme elevations did not exceed Grade 2. Through the long-term follow-up evaluation, as of the data cut-off date, including patients who reached 44 months, any event leading to death (n=4) was related to the progression of the patients’ underlying cardiovascular disease, consistent with what is expected for this patient population.
Nex-z is being further evaluated in patients with ATTR amyloidosis in the ongoing global Phase 3 MAGNITUDE and MANGITUDE-2 clinical trials for ATTR-CM and hereditary ATTR amyloidosis with polyneuropathy, respectively. On October 29, 2025, the United States Food and Drug Administration placed a clinical hold on the investigational new drug applications for the MAGNITUDE and MAGNITUDE-2 trials.
Forward-Looking Statements
This Current Report on Form 8-K and certain of the materials furnished or filed herewith contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
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 lonvoguran ziclumeran or “lonvo-z” (f/k/a NTLA-2002) for hereditary angioedema (“HAE”) and nexiguran ziclumeran or “nex-z” (f/k/a NTLA-2001) for transthyretin (“ATTR”) amyloidosis, including the ability to successfully complete its global Phase 3 HAELO study of lonvo-z for HAE and to address the clinical hold that the United States Food and Drug Administration (“FDA”) placed on the investigational new drug (“IND”) applications for its global Phase 3 MAGNITUDE study of nex-z for ATTR amyloidosis with cardiomyopathy (“ATTR-CM”) and its global Phase 3 MAGNITUDE-2 study for hereditary ATTR amyloidosis with polyneuropathy (“ATTRv-PN”) to resume the MAGNITUDE and MAGNITUDE-2 clinical trials; its ability to present a topline data readout from the HAELO study by mid-2026; lonvo-z’s potential to become a one-time treatment for HAE; and nex-z’s potential to become a one-time treatment for ATTR amyloidosis.
Any forward-looking statements in this current report on Form 8-K 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 lonvo-z and 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, including risks related to our ability to complete the Phase 3 HAELO study for HAE, present a topline data readout from the HAELO study by mid-2026, generate data to support lonvo-z’s potential to be a one-time treatment for HAE, address the clinical hold that the FDA placed on the IND applications for the MAGNITUDE Phase 3 study for ATTR-CM and the MAGNITUDE-2 Phase 3 study for ATTRv-PN and to resume those clinical trials; the risk that any one or more of Intellia’s product candidates, including lonvo-z and 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 current report on Form 8-K is as of the date of the report, and Intellia undertakes no duty to update this information unless required by law.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit |
Description | |
| 99.1 | Press Release dated November 8, 2025 titled “Intellia Therapeutics Presents Positive Pooled Phase 1/2 Data of Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angiodema” | |
| 99.2 | Press Release dated November 10, 2025 titled “Intellia Therapeutics Presents Positive Longer-Term Phase 1 Data of Nexiguran Ziclumeran (nex-z) in Patients with Transthyretin (ATTR) Amyloidosis with Cardiomyopathy” | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| Intellia Therapeutics, Inc. | ||||||
| Date: November 10, 2025 | By: | /s/ John M. Leonard | ||||
| Name: John M. Leonard | ||||||
| Title: Chief Executive Officer and President | ||||||
Exhibit 99.1
Intellia Therapeutics Presents Positive Pooled Phase 1/2 Data of Lonvoguran
Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema
November 8, 2025
| • | Deep, stable and durable reductions in kallikrein observed |
| • | Among 32 patients who received a 50 mg dose of lonvo-z as of data cutoff: |
| • | 31 (97%) were attack-free and long-term prophylaxis (LTP)-free |
| • | 24 (75%) were attack-free and LTP-free for at least seven months (up to 32 months) |
| • | Among the 11 patients who originally received a 50 mg dose in Phase 2, 10 were attack-free and LTP-free |
| • | Continue to observe a well-tolerated safety profile with up to three years of patient follow-up and no new long-term risks identified |
CAMBRIDGE, Mass., Nov. 08, 2025 (GLOBE NEWSWIRE) – Intellia Therapeutics, Inc. (NASDAQ: NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today presented positive clinical data from a pooled analysis of all patients who received a 50 milligram (mg) dose of lonvo-z in the company’s ongoing Phase 1/2 clinical trial in patients with hereditary angioedema (HAE). These results were shared in an oral presentation today at the American College of Allergy, Asthma & Immunology (ACAAI) 2025 Annual Scientific Meeting in Orlando, Florida.
“Today’s data further support our belief that lonvo-z could completely redefine the HAE treatment landscape,” said Intellia President and Chief Executive Officer John Leonard, M.D. “With up to three years of follow-up, the vast majority of patients who received a one-time 50 mg dose of lonvo-z – including 10 of our original 11 patients who received this dose in Phase 2 – were both attack-free and LTP-free as of the data cutoff. We are looking forward to our approaching topline readout from our Phase 3 HAELO clinical trial by mid-2026.”
“Hereditary angioedema is a condition with significant burden that is marked by the unpredictable nature of when the next attack could occur, the painful and often prolonged swellings themselves as well as the need for lifelong treatment,” said Dr. Danny Cohn, M.D., Ph.D., Internist, Department of Vascular Medicine, Amsterdam University Medical Center. “The data presented today offer hope that lonvo-z could significantly reduce or remove those burdens for many patients via a one-time treatment. I am eagerly awaiting results from the ongoing HAELO Phase 3 clinical trial.”
| Page 1 of 5 | intelliatx.com |
Pooled Phase 1/2 Analysis
Intellia’s global Phase 1/2 clinical trial is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of lonvo-z in adults with HAE Types I or II. Today’s presentation was based on a pooled analysis of all 32 patients who have received a one-time 50 mg treatment of lonvo-z via intravenous infusion in the Phase 1/2 trial. Of the 32 patients, 15 had initially received the 50 mg dose at study Day 1 (four in Phase 1 and 11 in Phase 2) and 17 were treated after unblinding of the Phase 2 clinical trial for the primary analysis (11 had originally received a 25 mg dose of lonvo-z, which was determined to be a suboptimal dose, and six had previously received placebo). The data cut-off for the analysis was August 29, 2025.
Deep, stable and durable reductions in plasma kallikrein were observed in all patients, with a mean reduction of 89% at month 24. Among the 32 patients, 31 (97%) were both attack-free and LTP-free as of the data cutoff, with 24 (75%) being attack-free and LTP-free for at least seven months (up to 32 months for patients with the longest follow-up). Of the 11 patients who initially received the 50 mg dose of lonvo-z in Phase 2, 10 were attack-free and LTP-free (nine for 7-32 months and one for <6 months). The one patient who was not attack-free and LTP-free as of the data cutoff had a 59% reduction from baseline in their monthly attack rate.
Safety
After a 50 mg dose, a well-tolerated safety profile was observed for up to three years of follow-up with no long-term risks identified. The most frequent treatment-emergent adverse events (TEAEs) within 28 days of infusion were infusion-related reactions, fatigue and headache. The most frequent TEAEs reported ≥28 days after infusion up to long-term follow-up (LTFU) were nasopharyngitis, upper respiratory tract infection, back pain, arthralgia and COVID-19. A single Grade 2 AST elevation was reported among all patients who received a 50 mg dose of lonvo-z. This event had an onset at Day 1 and spontaneously resolved by Day 4 in a patient previously treated with lonvo-z 25 mg. Safety of the 50 mg dose after patients received the suboptimal dose (25 mg) was consistent with the overall clinical trial population. There were no clinically significant shifts in liver enzymes or coagulation parameters. One serious adverse event (SAE), a pulmonary embolism, was observed in a patient with multiple risk factors one year after the infusion, and the event resolved without sequelae. In LTFU (n=17), there were no SAEs or TEAEs reported with 50 mg of lonvo-z, as of the data cutoff.
A one-time 50 mg treatment of lonvo-z is being further evaluated in patients with HAE in the ongoing global Phase 3 HAELO clinical trial that completed enrollment in September 2025.
The ACAAI data presentation will be available on the Scientific Publications & Presentations section of intelliatx.com.
| Page 2 of 5 | intelliatx.com |
About the Lonvoguran Ziclumeran (lonvo-z, formerly known as NTLA-2002) Clinical Program
Intellia’s ongoing Phase 1/2 clinical trial is evaluating the safety and efficacy of lonvo-z in adults with Type I or Type II hereditary angioedema (HAE). The Phase 1 portion is an international, open-label trial designed to identify the dose level of lonvo-z selected for further evaluation in the Phase 2 portion of the trial. Enrollment in both portions of the Phase 1/2 trial is complete. Intellia completed enrollment in the global Phase 3, randomized, double-blind, placebo-controlled HAELO clinical trial in September of 2025. Visit clinicaltrials.gov (NCT05120830) for more details.
About Lonvo-z
Based on Nobel Prize-winning CRISPR/Cas9 technology, lonvo-z has the potential to become the first one-time treatment for hereditary angioedema (HAE). Lonvo-z is an investigational in vivo CRISPR-based gene editing therapy that is currently being investigated in HAELO, a Phase 3 clinical trial in HAE, and is designed to prevent HAE attacks by inactivating the kallikrein B1 (KLKB1) gene, which encodes for prekallikrein, the kallikrein precursor protein. Interim Phase 1/2 clinical data showed dramatic reductions in attack rate, as well as consistent, deep and durable reductions in kallikrein levels. Lonvo-z has received five notable regulatory designations, including Orphan Drug and RMAT Designation by the U.S. Food and Drug Administration (FDA), the Innovation Passport by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), Priority Medicines (PRIME) Designation by the European Medicines Agency, as well as Orphan Drug Designation (ODD) by the European Commission.
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 concerning: the safety, efficacy, success and advancement of its clinical programs for lonvoguran ziclumeran or “lonvo-z” (f/k/a NTLA-2002) for hereditary angioedema (“HAE”), including the ability to successfully complete its global Phase 3 HAELO study and to present a topline data readout from the HAELO study by mid-2026; and lonvo-z’s potential to significantly reduce or remove burdens for patients with HAE and to become the first one-time treatment for HAE.
| Page 3 of 5 | intelliatx.com |
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 Intellia’s relationship with third parties, including its contract manufacturers, licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; 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 lonvo-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, including our ability to complete the Phase 3 HAELO study for HAE, present a topline data readout from the HAELO study by mid-2026, and generate data to support lonvo-z’s potential to significantly reduce or remove burdens for patients with HAE via a one-time treatment; the risk that any one or more of Intellia’s product candidates, including lonvo-z, will not be successfully developed and commercialized; and 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. 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 of 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.
| Page 4 of 5 | intelliatx.com |
Intellia Contacts:
Investors:
Jason Fredette
Vice President, Investor Relations and Corporate Communications
Intellia Therapeutics, Inc.
Media:
Matt Crenson
Ten Bridge Communications
# # #
| Page 5 of 5 | intelliatx.com |
Exhibit 99.2
Intellia Therapeutics Presents Positive Longer-Term Phase 1 Data of Nexiguran
Ziclumeran (nex-z) in Patients with Transthyretin (ATTR) Amyloidosis with
Cardiomyopathy
| • | One-time treatment of nex-z led to consistently rapid, deep and durable reduction in serum TTR through three years of follow-up |
| • | Consistent trend in disease stability or improvement in multiple measures of cardiomyopathy, regardless of NYHA Class, at 24 months compared to baseline |
| • | Longer-term safety data consistent with previously reported Phase 1 data |
CAMBRIDGE, Mass., Nov. 10, 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 positive follow-up data from the ongoing Phase 1 clinical trial of its investigational product nexiguran ziclumeran (nex-z) in patients with transthyretin (ATTR) amyloidosis with cardiomyopathy. Results were shared today in a late-breaking oral presentation at the American Heart Association (AHA) Scientific Sessions 2025 in New Orleans, Louisiana.
“These longer-term data showed a consistent and durable reduction in TTR and stability or improvement in multiple markers of cardiomyopathy following a single dose of nex-z,” said Intellia President and Chief Executive Officer John Leonard, M.D. “It’s remarkable that even in patients with advanced heart failure, a population that declines rapidly, disease stabilization or improvement was observed out to 24 months in a majority of participants. We look forward to seeing how these data mature in longer-term follow up. In addition, we are working diligently to address the ongoing clinical hold the FDA placed on our MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials.”
“ATTR amyloidosis is a progressive and fatal disease, often leaving patients with shortened lifespans and poor quality of life,” said Julian Gillmore, M.D., Ph.D., Professor of Medicine, National Amyloidosis Center, UCL Division of Medicine, Royal Free Hospital, U.K. “Today’s data support the potential benefit of nex-z and how persistently low levels of serum TTR may translate to improved outcomes and lowered rates of mortality.”
The Phase 1 clinical trial is an open-label, two-part trial evaluating the safety and efficacy of nex-z in patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM). The trial enrolled 36 patients, a high proportion of whom had advanced disease at baseline (50% classified as New York Heart Association (NYHA) Class III and 31% with variant ATTR-CM). Data presented today were as of an August 23, 2025, data cut-off date.
| Page 1 of 5 | intelliatx.com |
Continuation of Deep and Durable Serum TTR Reduction in Phase 1
Across all patients, a one-time treatment of nex-z led to consistently rapid, deep and sustained serum TTR reduction, regardless of baseline levels, through the latest follow-up. All patients continued to show a sustained response with no evidence of a waning effect over time. Among the nine patients who reached 36 months of follow-up, the mean serum TTR reduction was 87% (mean absolute serum TTR level of 22.9 µg/mL [mean 95% CI, 16.0 to 29.8]), consistent with the overall cohort at month 24. Based on multiple studies in ATTR amyloidosis, low levels of serum TTR have been shown to lead to a meaningful clinical benefit.
Evidence of Stability or Improvement on Clinical and Biomarker Measures in Phase 1
Patients dosed with nex-z continued to show evidence of disease stabilization or improvement at month 24 compared to baseline. Evaluation was based on multiple markers of cardiomyopathy, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hs-Troponin T), 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ) and echocardiographic measures.
At 24 months, NT-proBNP and hs-Troponin T, which are markers known to be associated with disease progression, showed stability or improvement in 70% and 85% of patients, respectively. Preservation of functional status, as measured by 6MWT, was observed with 69% of patients either showing stability or improvement. Notably, 81% of patients were stable or improved in their NYHA classification at 24 months, including improvement in 83% of patients with NYHA Class III. There also was evidence of benefit in quality of life, regardless of NYHA Class at baseline as assessed by KCCQ. Assessment of cardiac structure with echocardiography showed a similar pattern of stability with limited progression of cardiac remodeling at 24 months.
Post-Hoc Mortality Assessment of Phase 1 Data
Additionally, findings from a mortality assessment were presented. This post-hoc analysis was conducted on a cohort of 1,792 ATTR-CM patients from the National Amyloidosis Center (NAC) whose baseline characteristics were matched to those of the Phase 1 nex-z population. The analysis showed patients receiving a one-time treatment with nex-z had an all-cause mortality rate of 3.9 per 100 patient-years, while the matched cohort had an all-cause mortality rate of 12.7 per 100 patient-years (HR 0.27, p=0.009).
| Page 2 of 5 | intelliatx.com |
Phase 1 Safety
Nex-z was generally well tolerated across all patients in the Phase 1 clinical trial. The most commonly reported treatment-related adverse events were infusion-related reactions (IRRs) and transaminase elevations. In this Phase 1 population, liver enzyme elevations did not exceed Grade 2. Through the long-term follow-up evaluation, including patients who reached 44 months, any event leading to death (n=4) was related to the progression of the patients’ underlying cardiovascular disease, consistent with what is expected for this patient population.
The AHA data presentation will be available on the Scientific Publications & Presentations section of intelliatx.com.
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 with cardiomyopathy (ATTR-CM) and/or polyneuropathy (ATTRv-PN). 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. This investigational product is being investigated in the ongoing MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials in ATTR-CM and ATTRv-PN, respectively, which are currently on clinical hold by the U.S. Food and Drug Administration (FDA). Further information about the clinical hold can be found here. Nex-z has received Orphan Drug and RMAT Designations from the FDA and an Orphan Drug Designation (ODD) from the European Commission. 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.
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About Intellia Therapeutics
Intellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. The company’s in vivo programs use CRISPR to enable precise editing of disease-causing genes directly inside the human body. Intellia’s ex vivo programs use CRISPR to engineer human cells outside the body for the treatment of cancer and autoimmune diseases. 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, efficacy, success and advancement of its clinical programs for nexiguran ziclumeran or “nex-z” (f/k/a NTLA-2001), for transthyretin (“ATTR”) amyloidosis, including the ability to address the clinical hold that the United States Food and Drug Administration (“FDA”) placed on the investigational new drug (“IND”) applications for our global Phase 3 MAGNITUDE study for ATTR amyloidosis with cardiomyopathy (“ATTR-CM”) and our global Phase 3 MAGNITUDE-2 study for hereditary ATTR amyloidosis with polyneuropathy (“ATTRv-PN”), and to resume those clinical trials; and its belief that greater TTR reduction may lead to greater clinical benefit.
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, including
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risks related to our ability to address the clinical hold that the FDA placed on the IND applications for the MAGNITUDE Phase 3 study for ATTR-CM and the MAGNITUDE-2 Phase 3 study for ATTRv-PN and to resume those 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 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 form 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
Intellia Therapeutics, Inc.
Media:
Matt Crenson
Ten Bridge Communications
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