Intellia Therapeutics, Inc. · NASDAQ:NTLA

Intellia Therapeutics — American Heart Association Scientific Sessions 2025 (AHA25)

19 slides from Intellia Therapeutics's conference presentation, November 2025

  1. Slide 1: Updated Phase 1 Clinical Trial Outcomes of CRISPR Gene Editing With Nexiguran Ziclumeran

    Updated Phase 1 Clinical Trial Outcomes of CRISPR Gene Editing With Nexiguran Ziclumeran in Patients With Transthyretin Amyloidosis With Cardiomyopathy Julian D. Gillmore,1 Scott D. Solomon,2 Jörg Täubel,3 Ed Gane,4 Björn Pilebro,5 David Adams,6 Brian Claggett,2 Jessica Kachadourian,7 Ricardo Rocha,

  2. Slide 2: Disclosure

    Disclosure Dr. Gillmore reports consultancy agreements with Alexion Pharmaceuticals, Alnylam Pharmaceuticals, AstraZeneca, BridgeBio, Intellia Therapeutics, Ionis Pharmaceuticals, Lycia Therapeutics, Pfizer, and an institutional grant from Alnylam Pharmaceuticals 2

  3. Slide 3: ATTR amyloidosis is a progressive and fatal disease

    ATTR amyloidosis is a progressive and fatal disease ATTR amyloidosis with cardiomyopathy (ATTR-CM) is characterized by progressive cardiac remodeling and dysfunction, decline in functional capacity and QoL, frequent hospitalization, and death1 This process occurs much more rapidly in patients with a

  4. Slide 4: Nex-z is an in vivo investigational one-time CRISPR/Cas9 therapy designed to inactivate the TTR gene

    Nex-z is an in vivo investigational one-time CRISPR/Cas9 therapy designed to inactivate the TTR gene, whether wild-type or variant1,2 Nex-z is delivered as a one-time IV infusion over 2 to 4 hours Cas9, CRISPR-associated protein 9; CRISPR, clustered regularly interspaced short palindromic repeats; g

  5. Slide 5: Phase 1, two-part, open-label study of nex-z in adults with ATTR-CM

    Phase 1, two-part, open-label study of nex-z in adults with ATTR-CM Hereditary transthyretin amyloidosis with cardiomyopathy (ATTRv-CM) or wild-type cardiomyopathy (ATTRwt-CM), NYHA class I-III1 PART I – DOSING COMPLETE PART II Single-Ascending Dose Dose Expansion 1.0 mg/kg NYHA class I/II (n=3) Sym

  6. Slide 6: Demographics and baseline characteristics

    Demographics and baseline characteristics All patients All patients Characteristic Characteristic (N=36) (N=36) Age, median (min, max), y 78 (46, 90) TTR genotype, n (%) Sex, male, n (%) 35 (97) Wild type 25 (69) Black or African descent 8 (22) Race, n (%) p.V142Ia 7 (19) White or Caucasian 28 (78)

  7. Slide 7: One-time nex-z led to consistent rapid, deep, and durable reductions in serum TTR in patients with ATTR-CM

    One-time nex-z led to consistent rapid, deep, and durable reductions in serum TTR in patients with ATTR-CM 275 Absolute Serum TTR Absolute Serum TTR (μg/mL) 250 225 Mean (95% CI) 200 Baseline 194.8 (171.3 to 218.3) Serum TTR (μg/mL) 175 Mean (95% CI) Day 28 18.9 (15.4 to 22.5) 150 125 Month 24 26.0

  8. Slide 8: One-time nex-z led to durable reductions in serum TTR in ATTR-CM and ATTRv-PN

    One-time nex-z led to consistent rapid, deep, and durable reductions in serum TTR in patients with ATTR-CM and ATTRv-PN 275 Absolute Serum TTR 275 Recently Published: one-time nex-z 250 (patients with ATTR-CM) 250 administration in patients with ATTRv-PN1,a 225 225 200 200 Serum TTR (μg/mL) Serum TT

  9. Slide 9: One-time nex-z treatment led to stabilization of NT-proBNP, hs-troponin T, and 6MWT over 24 months

    One-time nex-z treatment led to stabilization of NT-proBNP, hs-troponin T, and 6MWT over 24 months NT-proBNP hs-Troponin T 6MWT Distance (meters) 2 Mean (95% CI) fold change at: 2 Mean (95% CI) fold change at: 100 Median (IQR) change at: • Month 12: 1.02 (0.88 to 1.17) • Month 12: 0.95 (0.89 to 1.01

  10. Slide 10: Improvement/stabilization of disease progression maintained regardless of NYHA class at baseline

    Improvement/stabilization of disease progression maintained regardless of NYHA class at baseline NT-proBNP hs-Troponin T 6MWT Distance (meters) 2 2 100 Fold Change From Baseline, Fold Change From Baseline, Change From Baseline, Geometric Mean (95% CI) Geometric Mean (95% CI) 60 1.5 1.5 Median (IQR)

  11. Slide 11: One-time nex-z stabilized or improved functional status and symptom severity

    One-time nex-z stabilized or improved functional status and symptom severity Change from Baseline in NYHA Class at Month 24a 70 60 50 % of Patients 40 30 20 10 0 NYHA Class I/II NYHA Class III Overall (n=18) (n=18) (N=36) Improved Stable Progressed 81% of patients demonstrated either no change or im

  12. Slide 12: One-time nex-z stabilized or improved QoL, regardless of NYHA class at baseline

    One-time nex-z stabilized or improved QoL, regardless of NYHA class at baseline Change from Baseline in KCCQ-OS Through Month 24 All Patients NYHA Class I/II vs Class III 20 20 Change From Baseline, Change From Baseline, 10 10 Median (IQR) Median (IQR) Improvement Improvement 0 0 Month 12: 7.8 (-0.5

  13. Slide 13: Echocardiographic assessments of cardiac remodeling showed a similar pattern of stability for 24 months

    Echocardiographic assessments of cardiac remodeling showed a similar pattern of stability for 24 months following nex-z treatment 4 LV Wall Thickness, mm 4 Septum Wall 45 Atrial Size, mL 4 Global Longitudinal Thickness, mm Strain, % Change From Baseline, Change From Baseline, 30 Change From Baseline

  14. Slide 14: Evaluation of mortality in patients treated with nex-z compared with a matched cohort of patients

    Evaluation of mortality in patients treated with nex-z compared with a matched cohort of patients Patients With ATTR-CM Matched Treated with • A cohort of ATTR-CM patients from the National Characteristica cohort nex-z P value Amyloidosis Centre (NAC) who were not receiving (N=1751) (N=36) stabilize

  15. Slide 15: All-cause mortality rate in patients treated with nex-z was ~3-fold lower than in a matched cohort

    All-cause mortality rate in patients treated with nex-z was ~3-fold lower than that observed in a matched cohort of patients Death From Any Cause Nex-z mortality rate: 3.9 (1.5, 10.5) per 100py Survival probability Matched cohort mortality rate: 12.7 (11.4, 14.2) per 100py HR: 0.27 (0.10, 0.73), P=0

  16. Slide 16: Phase 1 ATTR-CM safety summary

    Phase 1 ATTR-CM safety summary Event n (%) At least one AE 36 (100) AEs occurring in ≥15% of patients In this Phase 1 Trial Cardiac failure 13 (36) • Nex-z was generally well tolerated with IRRs being the most COVID-19 8 (22) frequent related AE Upper respiratory tract infection 7 (19) Atrial fibril

  17. Slide 17: Conclusions

    Conclusions • In this Phase 1 study, nex-z was generally well tolerated with IRRs being the most frequent treatment-related AE • A one-time treatment with nex-z yielded rapid, consistent, deep, and durable reductions in TTR in patients with ATTR-CM • Compared with the natural history of disease, nex

  18. Slide 18: Acknowledgments

    Acknowledgments We wish to extend our gratitude to:​ • The patients, their caregivers, and their families​ • My co-investigators and the study site staff This study was sponsored by Intellia Therapeutics and Regeneron Pharmaceuticals. Medical writing and editorial support were provided by Gretchen C

  19. Slide 19: THANK YOU

    THANK YOU 333 Scientific ‘=? Sessions #AHA25

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