Executive Brief

  • Intellia Therapeutics announced positive longer-term Phase 1 clinical data for nexiguran ziclumeran (nex-z, NTLA-2001) in hereditary transthyretin (ATTR) amyloidosis with polyneuropathy (ATTRv-PN) (Item 7.01, 8.01).
  • At 24 months post single dose ≥0.3 mg/kg (n=33), mean serum TTR reduction was 92%; at 36 months (n=12), reduction was 90% (Item 8.01).
  • Clinical measures (mNIS+7, NIS, mBMI, QoL-DN, NfL, PND) showed stability or improvement in most patients, including those who progressed on patisiran (Item 8.01).
  • Nex-z was generally well tolerated; infusion-related reactions were mild/moderate; three Grade ≥3 liver enzyme elevations resolved without intervention (Item 8.01).
  • Phase 3 MAGNITUDE-2 trial initiated April 2025, enrolling ~50 patients randomized 1:1 to 55 mg nex-z or placebo; enrollment expected complete H1 2026 (Item 8.01).
  • Intellia anticipates submitting biologics license application (BLA) for ATTRv-PN by 2028 (Item 8.01).
  • Forward-looking statements caution on risks including clinical, regulatory, intellectual property, and collaboration uncertainties (Item 7.01, 8.01).
  • No financial data or governance changes disclosed.
  • Information is new and not previously announced (implied by filing context).
  • Press release furnished as Exhibit 99.1 (Item 7.01).

Item-by-Item Analysis

Item 7.01 – Regulation FD Disclosure

  • What happened: Intellia issued a press release on September 25, 2025, announcing positive longer-term Phase 1 data for nex-z in ATTRv-PN patients.
  • Source: (Item 7.01, para 1), (Exhibit 99.1).

Item 8.01 – Other Events

  • What happened: Detailed clinical data update on Phase 1 trial of nex-z and Phase 3 MAGNITUDE-2 trial status.
  • Clinical facts:
    • Data cutoff: April 11, 2025.
    • Patients dosed ≥0.3 mg/kg: 33.
    • Mean serum TTR reduction at 24 months: 92% (mean absolute 17.3 µg/mL; 95% CI 12.5–22.2).
    • At 36 months (n=12): 90% reduction (mean absolute 20 µg/mL; 95% CI 11.2–28.8).
    • Clinical endpoints: 72% (13/18) showed ≥4 point improvement in mNIS+7 at 24 months.
    • Secondary endpoints (mBMI, QoL-DN, NfL) trended toward improvement.
    • 89% showed improvement or stability in PND scores through 24 months.
    • Safety: Generally well tolerated; infusion-related reactions mild/moderate; 3 Grade ≥3 liver enzyme elevations asymptomatic, resolved without intervention.
  • Phase 3 MAGNITUDE-2 trial:
    • Design: randomized, double-blind, placebo-controlled.
    • Patients: ~50, randomized 1:1 to 55 mg nex-z or placebo.
    • Dosing started April 2025.
    • Enrollment expected complete first half 2026.
  • Regulatory plan: BLA submission anticipated by 2028.
  • Source: (Item 8.01, paras 1–7).

Item 9.01 – Financial Statements and Exhibits

  • Exhibits:
    • 99.1 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.”
  • Source: (Item 9.01).

Exhibits Summary

  • Exhibit 99.1: Press release provides detailed clinical data, safety profile, Phase 3 trial update, and regulatory outlook consistent with the 8-K body text.

Financial & Dilution Impact

  • Unknown; no financial guidance, charges, or share issuance disclosed.

Timeline & Required Actions

  • Phase 3 MAGNITUDE-2 enrollment completion expected H1 2026.
  • BLA submission targeted by 2028.

Risks & Monitoring

  • Risks include clinical trial success, regulatory approvals, intellectual property protection, and collaboration continuity.
  • Monitor Phase 3 trial enrollment progress and data readouts.
  • Watch for regulatory feedback and BLA submission timing.

Metadata & Quality Checks

  • No OCR or formatting issues detected.
  • Non-GAAP reconciliation: Unknown.
  • Forward-looking statements present (Item 7.01, 8.01).
  • No conflicts or related-party transactions disclosed.

Final Checklist

  • Identified Items 7.01, 8.01, 9.01.
  • Extracted clinical and trial data with dates and patient counts.
  • Noted forward-looking statements and risk disclosures.
  • Summarized press release as Exhibit 99.1.
  • No financial or governance changes reported.
  • Provided timeline and next steps.
  • Highlighted key risks and monitoring points.

Original Filing