NTLA shows ~90% TTR reduction through 36 months for nex-z in Phase 1

Rhea-AI Filing Summary

Intellia Therapeutics reported interim clinical data for its in vivo CRISPR gene editing therapy "nex-z" (NTLA-2001) in hereditary transthyretin (ATTR) amyloidosis with polyneuropathy. In an open-label Phase 1 study, a one-time dose at or above 0.3 mg/kg (n=33) produced a mean serum TTR reduction of 92% at 24 months, corresponding to a mean absolute TTR level of 17.3 µg/mL (95% CI 12.5–22.2). Among 12 patients followed to 36 months, mean reduction was 90% with a mean absolute level of 20 µg/mL (95% CI 11.2–28.8).

Clinical measures such as quality-of-life for diabetic neuropathy (QoL-DN) and neurofilament light chain (NfL) trended toward improvement, and 89% of patients showed improvement or stability in PND scores through 24 months versus baseline. The filing also reiterates standard development and collaboration risks, including regulatory and development uncertainties and reliance on partners.

Positive

• Durable biochemical effect: Mean serum TTR reduction of 92% at 24 months for doses ≥0.3 mg/kg (n=33).
• Sustained response at 36 months: Mean serum TTR reduction of 90% among patients with longer follow-up (n=12).
• Clinical trends positive: QoL-DN and NfL trended toward improvement and 89% of patients showed improvement or stability in PND scores through 24 months.
• One-time dosing: Evidence of long-term effect after a single administration supports potential for a one-time therapeutic approach.

Negative

• Limited sample size for long-term data: Only 12 patients reached 36-month follow-up, limiting robustness of durability conclusions.
• Open-label Phase 1 design: Lack of control arm limits assessment of clinical efficacy versus placebo or comparator.
• Regulatory and development risks: Filing reiterates uncertainties around approvals, trial conduct, and reliance on collaborations which could delay development or commercialization.
• Incomplete safety context: The provided excerpt focuses on efficacy metrics and trends; comprehensive long-term safety data are not detailed in the content provided.

Insights

Clinical Development Analyst

TL;DR: Durable, large reductions in serum TTR through 24–36 months suggest sustained on-target activity from a one-time CRISPR therapy.

The reported mean serum TTR reductions of ~90–92% at 24 and 36 months indicate durable target knockdown after a single administration in the Phase 1 cohort. Absolute TTR levels (mean ~17–20 µg/mL) with stated 95% CIs demonstrate persistent biochemical effect across patients evaluated long-term. The reported trends in QoL-DN and NfL and the 89% rate of improved/stable PND scores support potential clinical benefit, though open-label Phase 1 data lack a control arm and patient numbers at 36 months (n=12) are limited. These results warrant accelerated development but require confirmatory controlled data on efficacy and safety in larger cohorts.

Regulatory/Risk Analyst

TL;DR: Data are promising for regulatory discussions, but material uncertainties remain around confirmatory trials and collaborations.

The substantial and durable biochemical response strengthens Intellia's position in regulatory interactions, potentially supporting pivotal study design discussions. However, the filing emphasizes risks including uncertainties in initiating and conducting studies, regulatory approvals, and reliance on collaborations. Investors should note that Phase 1 open-label outcomes do not substitute for randomized Phase 3 evidence required for approval; operational and partner-related risks could materially affect timelines and commercialization prospects.

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 OR 15(d)

of The Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): September 25, 2025

INTELLIA THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

Delaware		001-37766		36-4785571
(State or other jurisdiction of incorporation)		(Commission File Number)		(IRS Employer Identification No.)

40 Erie Street, Suite 130 Cambridge, Massachusetts		02139
(Address of principal executive offices)		(Zip Code)

Registrant’s telephone number, including area code: (857) 285-6200

Not Applicable

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock (Par Value $0.0001)		NTLA		The Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 7.01 Regulation FD Disclosure.

On September 25, 2025, Intellia Therapeutics, Inc. (the “Company” or “Intellia”) issued a press release titled “Intellia Therapeutics Announces Positive Longer-Term Phase 1 Data for Nexiguran Ziclumeran (nex-z) in Patients with Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy.” 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.

The information under this Item 7.01, including Exhibit 99.1 hereto, is 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.

On September 25, 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 hereditary transthyretin (“ATTR”) amyloidosis with polyneuropathy (“ATTRv-PN”). 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 trial is an open-label study evaluating the safety and activity of nex-z in patients with ATTR amyloidosis.

As of the data cutoff date, which was April 11, 2025, deep, durable and consistent TTR reductions continue to be observed in the Phase 1 trial. 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 92% (corresponding mean absolute serum TTR level of 17.3 µg/mL [Mean 95% CI, 12.5 – 22.2]). Among the 12 patients who had reached 36 months of follow-up, the mean serum TTR reduction was 90% (corresponding mean absolute serum TTR level of 20 µg/mL [Mean 95% CI, 11.2 – 28.8]).

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, 13 (72%) showed improvements of a clinically meaningful threshold of ≥4 points, including most of the patients in the cohort who had progressed on patisiran. Among all 36 patients enrolled in the Phase 1 trial, mean values of the secondary endpoints mBMI, QoL-DN and NfL all trended toward disease improvement and 89% of patients showed improvement or stability in PND scores through 24 months compared to baseline.

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.

In addition, the Company provided an update on the Phase 3 MAGNITUDE-2 trial, which is a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of nex-z in approximately 50 patients, who are randomized 1:1 to receive a single 55 mg infusion of nex-z or placebo. The Company began dosing patients in MAGNITUDE-2 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 for ATTRv-PN by 2028.

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 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 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 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 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 No.		Description
99.1		Press release dated September 25, 2025.
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 hereunto duly authorized.

				Intellia Therapeutics, Inc.
						(Registrant)
Date: September 25, 2025				By:		/s/ John M. Leonard
						Name: John M. Leonard
						Title: Chief Executive Officer and President

FAQ

What efficacy results did Intellia (NTLA) report for nex-z in ATTR amyloidosis?

Intellia reported a mean serum TTR reduction of 92% at 24 months for doses ≥0.3 mg/kg (n=33) and a mean reduction of 90% at 36 months among 12 patients.

How durable is the effect of the one-time nex-z treatment?

The data show sustained biochemical effect with mean TTR reductions of ~90–92% through 24–36 months in the reported cohorts.

Did clinical measures show improvement in the trial?

QoL-DN and NfL trended toward improvement, and 89% of patients showed improvement or stability in PND scores through 24 months versus baseline.

Are there limitations to these results for NTLA's nex-z?

Yes. The results come from an open-label Phase 1 study with limited long-term sample size (36-month data in 12 patients) and lack a randomized control arm.

What risks did Intellia highlight in the filing?

Intellia reiterated risks including uncertainties in regulatory approvals and trial conduct, potential failure to develop or commercialize product candidates, and reliance on collaborations.