Slide 1: NTLA-2002 Long-Term Phase 1 Data Update from the Ongoing Phase 1/2 Study
NTLA-2002 Long-Term Phase 1 Data Update from the Ongoing Phase 1/2 Study June 3, 2024
Slide 2: Intellia Therapeutics' Legal Disclaimer
Intellia Therapeutics’ Legal Disclaimer This presentation contains “forward-looking statements” of Intellia Therapeutics, Inc. (“Intellia”, “we” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, exp
Slide 3: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Long-Term Phase 1 Data Dr. Hilary Longhurst Senior Medical Officer; Auckland District Health Board, Honorary Associate Professor; University of Auckland, New Zealand, trial’s principal inv
Slide 4: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Long-Term Phase 1 Data Dr. Hilary Longhurst Senior Medical Officer; Auckland District Health Board, Honorary Associate Professor; University of Auckland, New Zealand, trial’s principal inv
Slide 5: Advancing a Full-Spectrum Genome Editing Company
Advancing a Full-Spectrum Genome Editing Company CRISPR-Based Modular Platform EMPLOY NOVEL EDITING AND DELIVERY TOOLS In Vivo Ex Vivo CRISPR is CRISPR creates the therapy the therapy FIX THE TARGET GENE REW IRE & REDIRECT CELLS Genetic diseases Immuno-oncology Autoimmune diseases 5
Slide 6: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Long-Term Phase 1 Data Dr. Hilary Longhurst Senior Medical Officer; Auckland District Health Board, Honorary Associate Professor; University of Auckland, New Zealand, trial’s principal inv
Slide 7: CRISPR-Based Gene Editing of KLKB1 Resulted in Long-Term Plasma Kallikrein Protein Reduction
CRISPR-Based Gene Editing of KLKB1 Resulted in Long-Term Plasma Kallikrein Protein Reduction and Decreased Attack Rate in Patients With Hereditary Angioedema Updated Results From a Phase 1 Study Hilary Longhurst,1* Padmalal Gurugama,2 Karen Lindsay,1 Remy S. Petersen,3 Lauré M. Fijen,3 Carri Boisell
Slide 8: Disclosures
Disclosures Dr. Longhurst has acted as a consultant or speaker, received educational sponsorship or participated in research with BioCryst Pharmaceuticals, CSL Bering, Intellia Therapeutics, KalVista Pharmaceuticals, Pharming, and Takeda.
Slide 9: Targeting KLKB1 Gene Expression for Long-Term Prophylaxis of HAE Attacks
Targeting KLKB1 Gene Expression for Long-Term Prophylaxis of HAE Attacks Knocking out KLKB1 gene 1 is intended to prevent production of kallikrein Factor XII Factor XIIa C1-INH Decreasing kallikrein Prekallikrein Kallikrein 2 rebalances pathway by KLKB1 gene reducing bradykinin production HMW kinino
Slide 10: NTLA-2002 Mechanism of Action
Lipid nanoparticle NTLA-2002 Complementary KLKB1-specific sgRNA Mechanism of Action CA P ILLA RY sequence to KLKB1 gene Streptococcus pyogenes (Spy) NTLA-2002 Cas9 mRNA NTLA-2002 LDL receptors Uptake in Hepatocytes Endosomal release Endocytosis of LNP Endosome Cas9 sgRNA ribonucleotide protein Targe
Slide 11: NTLA-2002 Global Phase 1/2 Study Design and Eligibility Criteria
NTLA-2002 Global Phase 1/2 Study Design and Eligibility Criteria: Two-Part, Multicenter Study in Adults With HAE Types I and II KEY INCLUSION CRITERIA PHASE 1 PHASE 2 ✓ Documented diagnosis of Type I or Open-label, Expansion study to Type II HAE single-ascending dose confirm recommended dose ✓ At le
Slide 12: Patient Demographics and Characteristics
Patient Demographics and Characteristics 25 mg 50 mg 75 mg All Patients Parameter (n=3) (n=4) (n=3) (N=10) Age, years Median (range) 30 (26-52) 65 (52-73) 45 (27-49) 51 (26-73) Sex, n (%) Male 3 (100) 1 (25) 2 (67) 6 (60) Female – 3 (75) 1 (33) 4 (40) Weight, kg Median (range) 83 (78-135) 86 (74-107
Slide 13: NTLA-2002 Continues to Be Well-Tolerated Across All Dose Levels
NTLA-2002 Continues to Be Well-Tolerated Across All Dose Levels All 25 mg 50 mg 75 mg TEAEs Occurring in ≥2 Patients Patients (n=3) (n=4) (n=3) (N=10) Any TEAE 3 4 3 10 With a median follow-up time of 20.1 months: Infusion-related reaction 2 2 3 7 • No treatment-emergent AEs ≥ Grade 3 COVID-19 3 1 2
Slide 14: Durable Reductions in Plasma Kallikrein Protein Over Time
A Single Dose of NTLA-2002 Continues to Show Dose-Dependent and Durable Reductions in Plasma Kallikrein Protein Over Time 0 Kallikrein Protein % Change From Baseline -10 -20 -30 (Mean ± SD) -40 -60% -50 -60 -70 * -80 -88% -95% -90 * * -100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80
Slide 15: 98% Mean Reduction in Monthly HAE Attack Rate
A Single Dose of NTLA-2002 Led to a 98% Mean Reduction in Monthly HAE Attack Rate Through the Latest Follow-up Percentage Change from Baselinea Mean (SD) Attacks Requiring All Attacks Moderate-to-Severe Attacks On-Demand Treatment Weeks 1-16 -90% (17%) -82% (22%) -95% (8.2%) (Primary observation per
Slide 16: 8 of 10 Patients Have Been Attack-Free Since the End of the Primary Observation Period
8 of 10 Patients Have Been Attack-Free Since the End of the Primary Observation Period Administration of Attack Severity: Mild Moderate Severe Prophylaxis Withdrawal: Additional follow-up Historic NTLA-2002 from prior data cut*: monthly attack rate prior to Screening Primary Observation Period Post-
Slide 17: Latest Data Continue to Reinforce Potential of NTLA-2002 as a Functional Cure
Latest Data Continue to Reinforce the Potential of a Single Dose of NTLA-2002 to Be a Functional Cure for Patients With HAE • NTLA-2002 continues to be well-tolerated at all doses; all AEs were transient and either Grade 1 or 2 • NTLA-2002 resulted in dose-dependent and durable reductions in plasma
Slide 18: Acknowledgements
Acknowledgements We wish to extend our gratitude to: ▪ The patients, their caregivers, and their families ▪ Study site coordinators and staff ▪ The staff of Simbec-Orion for assistance with study management and operations support ▪ Ilia Antonino (employee of Intellia Therapeutics) and Apollo Medical
Slide 19: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Long-Term Phase 1 Data Dr. Hilary Longhurst Senior Medical Officer; Auckland District Health Board, Honorary Associate Professor; University of Auckland, New Zealand, trial’s principal inv
Slide 20: NTLA-2002 Clinical Development Plan and Next Steps
NTLA-2002 Clinical Development Plan and Next Steps PHASE 1 PHASE 2 PHASE 3 ✓ 8 of 10 patients have been ✓ Fully enrolled o Initiate pivotal study attack-free in post-primary in 2H 2024 Poised to launch observation period o Present topline first-ever in vivo results mid-year 2024 o Submit BLA in 2026
Slide 21: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Long-Term Phase 1 Data Dr. Hilary Longhurst Senior Medical Officer; Auckland District Health Board, Honorary Associate Professor; University of Auckland, New Zealand, trial’s principal inv
Slide 22: HAE Market is Rapidly Growing and Expected to Reach $6B by 2029
HAE Market is Rapidly Growing and Expected to Reach $6B by 2029 Worldwide Sales For HAE Therapies1 7.0 $6.0B Current Leading Branded 6.0 Prophylaxis Therapies $5.0B 5.0 Administration2 Highest Drug $ Billions $4.3B 4.0 $3.7B Takhzyro® 1-2 SQ injections / month $3.3B $3.1B 2023 Sales $2.9B 3.0 Haegar
Slide 23: Significant Enthusiasm for NTLA-2002 Expressed by Physicians and Patients
Significant Enthusiasm for NTLA-2002 Expressed by Physicians and Patients REDUCED ATTACK FREQUENCY ONE-TIME SAFETY & COMPLETE DOSING RESPONSE Strong interest in Excitement about Physicians indicated long-term efficacy and one-time dosing satisfaction with target dramatic reduction addresses a key un
Slide 24: Well-Defined HAE Patient Segments Expected to Drive NTLA-2002 Commercial Uptake
Well-Defined HAE Patient Segments Expected to Drive NTLA-2002 Commercial Uptake SIGNIFICANT OPPORTUNITY ACROSS ALL PATIENT SEGMENTS 150K+ HAE patients 15-20% 40-55% 25-30% worldwide1 of patients are of patients on prophylaxis of patients currently avoid inadequately managed on treatments are general
Slide 25: High Lifetime Cost of Branded HAE Prophylaxis Therapies Makes One-Time Treatment Attractive to Payors
High Lifetime Cost of Branded HAE Prophylaxis Therapies Makes a One-Time Treatment Attractive to Payors Long-term prophylaxis annual treatment costs ~$140K – 450K 20 YEARS OLD $450K – 650K annually in key average age of annually in the U.S.1 European markets1 diagnosis 2 leads to decades of treatmen
Slide 26: A functional cure for people living with HAE
WHERE WE ARE TODAY…. WHERE WE THINK WE’RE HEADED… HAE patients are seeking improved efficacy and convenience to be free from disease and chronic treatment Long-term data from 10 patients reinforces the potential of NTLA-2002 to eliminate attacks after a one-time treatment A functional cure for peopl
Slide 27: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Long-Term Phase 1 Data Dr. Hilary Longhurst Senior Medical Officer; Auckland District Health Board, Honorary Associate Professor; University of Auckland, New Zealand, trial’s principal inv
Slide 28: Q&A NTLA-2002 Phase 1 Clinical Data Update
Q&A NTLA-2002 Phase 1 Clinical Data Update
Slide 29: Intellia Therapeutics
Inte:zia THERAPEUTICS