Intellia Therapeutics, Inc. · NASDAQ:NTLA
Intellia Therapeutics — Technical Presentation (June 2023)
32 slides from Intellia Therapeutics's technical presentation, Jun 12, 2023
Slide 1: NTLA-2002 Interim Clinical Data Update from Ongoing First-in-Human Study
NTLA-2002 Interim Clinical Data Update from Ongoing First-in-Human Study June 12, 2023 Shanna Living with hereditary angioedema
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 Interim Clinical Data Dr. David Lebwohl Chief Medical Officer, Intellia Therapeutics Overview of Current HAE Treatment Landscape and Unmet Medical Need Dr. Timothy J. Craig Tenured Profess
Slide 4: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Interim Clinical Data Dr. David Lebwohl Chief Medical Officer, Intellia Therapeutics Overview of Current HAE Treatment Landscape and Unmet Medical Need Dr. Timothy J. Craig Tenured Profess
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 REWIRE & 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 Interim Clinical Data Dr. David Lebwohl Chief Medical Officer, Intellia Therapeutics Overview of Current HAE Treatment Landscape and Unmet Medical Need Dr. Timothy J. Craig Tenured Profess
Slide 7: NTLA-2002 for Hereditary Angioedema (HAE)
NTLA-2002 for Hereditary Angioedema (HAE) About HAE Our Approach Key Advantages • Genetic disease characterized Knock out KLKB1 gene with Potential to: by recurring, severe and a single dose • Be a single-dose treatment unpredictable swelling in various parts of the body • Reduce kallikrein activity
Slide 8: NTLA-2002 is a novel, investigational CRISPR/Cas9-based in vivo gene editing therapy
Lipid nanoparticle NTLA-2002 is a novel, Complementary KLKB1-specific sgRNA investigational CAPILLARY sequence to KLKB1 gene CRISPR/Cas9-based Streptococcus NTLA-2002 in vivo gene editing pyogenes (Spy) Cas9 mRNA therapy NTLA-2002 Uptake in LDL receptors Hepatocytes Endosomal release Endocytosis of
Slide 9: NTLA-2002 global Phase 1/2 study design
NTLA-2002 global Phase 1/2 study design: Two-part, multi-center study of NTLA-2002 in adults with HAE Types I and II PHASE 1 PHASE 2 Open-label, Expansion study to single-ascending dose confirm recommended dose Intervention: Randomized Single dose 25 mg (n=3) 25 mg (n=10) administered via 50 mg (n=4
Slide 10: Key eligibility criteria (Phase 1)
Key eligibility criteria (Phase 1) INCLUSION EXCLUSION ✓ Documented diagnosis of Type I or x Concomitant use of ecallantide or Type II HAE lanadelumab ✓ At least 3 investigator-confirmed HAE x Known hypersensitivity or prior infusion- attacks within 90 days prior to screening related reaction to LNP
Slide 11: Patient demographics & characteristics
Patient demographics & characteristics 25 mg 50 mg 75 mg All patients Parameter n=3 n=4 n=3 N = 10 Age, years 30 (26-52) 65 (52-73) 45 (27-49) 51 (26-73) Median (range) Sex, n (%) Male 3 (100) 1 (25) 2 (67) 6 (60) Female – 3 (75) 1 (33) 4 (40) Weight, kg 83 (78-135) 86 (74-107) 72 (64-84) 83 (64-135
Slide 12: NTLA-2002 was generally well-tolerated across all dose levels evaluated
NTLA-2002 was generally well-tolerated across all dose levels evaluated Adverse events 25 mg 50 mg 75 mg All patients occurring in ≥ 2 n=3 n=4 n=3 N = 10 patients Gr. 1 Gr. 2 Gr. 1 Gr. 2 Gr. 1 Gr. 2 Gr. 1 Gr. 2 Any TEAE (max grade) 2 1 2 1 1 2 5 4 Infusion-related reaction 2 – 1 1 2 1 5 2 Fatigue 1
Slide 13: Dose-dependent and durable reductions in plasma kallikrein protein
NTLA-2002 resulted in dose-dependent and durable reductions in plasma kallikrein protein Data are mean values with standard deviation. 13 Dashed line represents targeted minimum reduction. Mean percentage reduction callout on graph refers to last measurement as of the data cutoff date.
Slide 14: Robust and durable HAE attack reductions observed in all patients after a single dose
Robust and durable HAE attack reductions observed in all patients after a single dose of NTLA-2002 Historic Administration of ATTACK SEVERITY: Mild Moderate Severe PROPHYLAXIS WITHDRAWAL: Longest monthly attack NTLA-2002 attack free rate prior to duration post screening SCREENING WK 16 NTLA-2002 Pt.
Slide 15: Robust and durable HAE attack reductions observed in all patients after a single dose
Robust and durable HAE attack reductions observed in all patients after a single dose of NTLA-2002 Historic Administration of ATTACK SEVERITY: Mild Moderate Severe PROPHYLAXIS WITHDRAWAL: Longest monthly attack NTLA-2002 attack free rate prior to duration post screening SCREENING WK 16 NTLA-2002 Pt.
Slide 16: Robust and durable HAE attack reductions observed in all patients after a single dose
Robust and durable HAE attack reductions observed in all patients after a single dose of NTLA-2002 Historic Administration of ATTACK SEVERITY: Mild Moderate Severe PROPHYLAXIS WITHDRAWAL: Longest monthly attack NTLA-2002 attack free rate prior to duration post screening SCREENING WK 16 NTLA-2002 Pt.
Slide 17: Single dose led to a 95% mean reduction in monthly HAE attack rate
Across all patients, a single dose of NTLA-2002 led to a 95% mean reduction in monthly HAE attack rate through the latest follow-up 25 mg 50 mg 75 mg All patients n=3 n=4 n=3 N = 10 Week 1-16 -91% (16%) -97 (5%) -80% (30%) -89 (19%) Week 5-16 -89% (19%) -100% (0%) -87% (23%) -92% (16%) Week 1-24 -94
Slide 18: Extended Phase 1 data reinforce the potential of NTLA-2002 to be a functional cure
Extended Phase 1 data reinforce the potential of NTLA-2002 to be a functional cure for people living with HAE • Robust and durable attack reductions observed in all patients after a single dose of NTLA-2002 – Across all patients, a single dose of NTLA-2002 led to 95% mean reduction in monthly HAE at
Slide 19: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Interim Clinical Data Dr. David Lebwohl Chief Medical Officer, Intellia Therapeutics Overview of Current HAE Treatment Landscape and Unmet Medical Need Dr. Timothy J. Craig Tenured Profess
Slide 20: The Future of Hereditary Angioedema
The Future of Hereditary Angioedema Timothy Craig, FAACAI, FAAAAI, FACP, FACOI Tenured Professor Medicine, Pediatrics, Biomedical Sciences Penn State University Distinguished Educator Director – ACARE Center of Excellence for Angioedema Director – Alpha-1-Antitrypsin Deficiency Center Medical Adviso
Slide 21: Conflicts of Interest
Conflicts of Interest Company Research Consultant Speaker Travel CSL Behring x x x x Ionis x x Takeda x x x x Biocryst x x BioMarin x x x Kalvista x x Pharvaris x Intellia x x x x 21
Slide 22: Clinical Presentation of HAE
Clinical Presentation of HAE 22
Slide 23: Evolution of HAE Treatment: A Tale of Generations Over Years
Evolution of HAE Treatment: A Tale of 3 Generations Over 16 Years • Pre-2008 → Grandmother – Rescue: Fresh Frozen Plasma – required ED administration; unreliable results – Prophylaxis: Androgens – required yearly assessment for toxicity; ill advised to use in females • 2008-2018 → Mother – Rescue: S
Slide 24: FDA-Approved On-Demand Therapeutic Options
FDA-Approved On-Demand Therapeutic Options Self Therapy Patients Administered Mechanism Notable Adverse Events Ecallantide ≥12 years of age No (sc) Inhibits plasma kallikrein Uncommon antidrug antibodies, risk of anaphylaxis Icatibant ≥18 years of age* Yes (sc) Bradykinin B2 receptor antagonist Comm
Slide 25: First-Line Long-Term Prophylactic Therapeutic Options
First-Line Long-Term Prophylactic Therapeutic Options Most Common Therapy Patients Approved Recommended Dose Adverse Events C1-INH Plasma-derived (iv) ≥6 years of age Pediatric: 500 U every 3 to 4 days Headache, nausea, rash, vomiting, and fever Adolescents/adults: 1000 U every 3 to 4 days (may incr
Slide 26: Rationale for the Development of New HAE Therapies
Rationale for the Development of New HAE Therapies • Improve treatment and outcomes for patients with HAE – Increased efficacy – Improved tolerability – Longer lasting prophylactic treatments • Reduction in treatment burden – Improved accessibility – Less frequent dosing – Improved quality of life F
Slide 27: Before Control
Before Control 27
Slide 28: After Control
After Control 28
Slide 29: Future of HAE Treatment
Future of HAE Treatment • In the past, we focused on treating attacks • Today, we focus on preventing attacks • Newer medications in development aim to have increased efficacy and less frequent or burdensome dosing and administration • My hope is that we are approaching a “relative cure” for HAE 29
Slide 30: Agenda
Agenda Welcome Introduction Dr. John Leonard Chief Executive Officer, Intellia Therapeutics Review of NTLA-2002 Interim Clinical Data Dr. David Lebwohl Chief Medical Officer, Intellia Therapeutics Overview of Current HAE Treatment Landscape and Unmet Medical Need Dr. Timothy J. Craig Tenured Profess
Slide 31: Q&A NTLA-2002 Interim Clinical Data Update
Q&A NTLA-2002 Interim Clinical Data Update
Slide 32: Intellia Therapeutics
Intezia THERAPEUTICS
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