Intellia Therapeutics, Inc. · NASDAQ:NTLA
Intellia Therapeutics — International Symposium on Amyloidosis (ISA) Meeting, Madrid, November 2-3, 2023
16 slides from Intellia Therapeutics's conference presentation, Nov 2, 2023
Slide 1: Enabling the development of serum [TTR] as a biomarker for treatment of ATTR amyloidosis
Exhibit 99.2 Enabling the development of November 2-3, 2023 • MADRID serum [TTR] as a biomarker for treatment of ATTR amyloidosis Julian D. Gillmore National Amyloidosis Centre, Division of Medicine, University College London on behalf of: 2 3 4 5 5 Jörg Täubel, Ed Gane, Björn Pilebro, Michael L. Ma
Slide 2: Disclosures
Disclosures • Adviser for Alnylam, AstraZeneca, Attralus, BridgeBio, Ionis, Pfizer, and Intellia
Slide 3: Treatment outcomes in systemic amyloidosis associate with residual amyloid precursor protein concentration
Treatment outcomes in systemic amyloidosis associate with 1,2 the residual concentration of the amyloid precursor protein 1 AA Amyloidosis Median SAA values >50 mg/L • More amyloid = worse outcomes Less amyloid = better outcomes • “Natural” clearance of in vivo amyloid deposits occurs slowly Baselin
Slide 4: Our community has incorporated this information to advance therapy in AA and AL amyloidosis
Our community has incorporated this information to advance therapy in AA and AL amyloidosis Specific concentration thresholds inform outcomes 1 AA amyloidosis 2 Unadjusted relative risk of death associated with the most recent AL amyloidosis a median annual SAA concentration during follow-up SAA Oct
Slide 5: Equilibrium between circulating amyloid fibril precursor protein and change in amyloid burden
There is an equilibTherape rium bet utic str ween ategies cir in cu am lat yloing idos amyl is oid fibril precursor protein Therapeutic strategies in amyloidosis concentration and change in amyloid burden Pr Precu ecur rso sor r p pr ro ote teiin n A Amyl mylo oiid d Precursor protein Amyloid Precur
Slide 6: Percent reduction in serum [TTR] is associated with clinical benefit in ATTR amyloidosis
Percent reduction in serum [TTR] is associated with clinical benefit in ATTR amyloidosis Pharmacodynamics: Primary endpoint: 1 1 % change in serum TTR over 18 months mNIS+7 neuropathy score Worse Better Median reduction in serum TTR in the patisiran group was 56% vs 4% 81% (range, -38% to 95%) and w
Slide 7: Should we be using residual absolute serum [TTR] instead of % reduction?
Serum [TTR] is typically expressed as % reduction from baseline – should we be using residual absolute serum [TTR] instead? % serum TTR reduction vs ΔmNIS+7 by Same % serum TTR reduction can mean nonile in APOLLO A different risk for ongoing fibril formation At the population level, ≈80% TTR lowerin
Slide 8: The NTLA-2001 phase 1 study in ATTR amyloidosis has completed enrollment (N=72)
The NTLA-2001 phase 1 study in ATTR amyloidosis has completed enrollment (N=72) Two-part, open-label, multicenter study in adults with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN) or ATTR amyloidosis with cardiomyopathy (ATTR-CM) PART I: Single-Ascending Dose Escalation PART II: Dose E
Slide 9: Patient demographics and characteristics
Patient demographics and characteristics Characteristic PN Patients (N=36) CM Patients (N=29) All Patients (N=65) Age, years Median (min, max) 61 (19, 75) 78 (46, 86) 68 (19, 86) Sex, n (%) Male 26 (72) 28 (97) 54 (83) Weight, kg Median (min, max) 77 (55, 117) 82 (63, 115) 81 (55, 117) p.V50M 11 (31
Slide 10: Most frequent treatment emergent adverse events
Most frequent treatment emergent adverse events TEAEs by Maximum Toxicity Grade and Preferred Term Reported in >5% of All ATTRv-PN and ATTR-CM Patients (N=65) • This includes all reported events, AE, Preferred Term, n (%) Any Grade Grade 1 Grade 2 Grade ≥3 including those unrelated to NTLA-2001 Infu
Slide 11: NTLA-2001 led to consistently low and sustained absolute serum [TTR] in all patients
Regardless of baseline TTR levels, NTLA-2001 led to consistently low and sustained absolute serum [TTR] in all patients 350 350 ATTR-CM ATTRv-PN NYHA I-II 0.7 mg/kg (N=3) 0.3 mg/kg (N=3) 300 300 NYHA III 0.7 mg/kg (N=6) 0.7 mg/kg (N=3) NYHA I-II 1.0 mg/kg (N=3) 1.0 mg/kg (N=6) Baseline IQR: Baseline
Slide 12: NTLA-2001 led to consistently low and sustained absolute serum [TTR] in all patients
Regardless of baseline TTR levels, NTLA-2001 led to consistently low and sustained absolute serum [TTR] in all patients The median (IQR) maximum change from day 28 onward (measure of fluctuations) = -1.4 µg/mL (-4.7 to 1.7) 350 350 ATTR-CM ATTRv-PN 300 NYHA I-II 0.7 mg/kg (N=3) 300 0.3 mg/kg (N=3) N
Slide 13: Summary
Summary • In other systemic amyloidoses, the residual, absolute concentration of the amyloid precursor protein is closely associated with clinical outcomes • Interim data from 62 patients with ATTR amyloidosis treated with NTLA-2001 continue to show a favorable safety and tolerability profile, with
Slide 14: Acknowledgments
Acknowledgments We extend our gratitude to the patients who United Kingdom participated in the NTLA-2001 Phase 1 study National Amyloidosis Centre and their family and caregiver networks Physicians Histology Staff executing the study on behalf of: Prof. Mariana Janet Gilbertson Richmond Pharmacology
Slide 15: Appendix
Appendix 41H ATR inylotdosis INTERNATIONAL Meetine
Slide 16: Dose-responsive rapid and deep serum TTR reduction sustained across all patients
Dose-responsive rapid and deep serum TTR reduction sustained across all patients 0.1 mg/kg (N=3) NYHA I-II 0.7 mg/kg (N=3) ATTR-CM ATTRv-PN 0.3 mg/kg (N=3) 0 0 NYHA III 0.7 mg/kg (N=6) 0.7 mg/kg (N=3) NYHA I-II 1.0 mg/kg (N=3) -10 -10 1.0 mg/kg (N=6) NYHA I-II 55 mg (N=11) 55 mg (N=16) NYHA III 55 m