Intellia Therapeutics, Inc. · NASDAQ:NTLA
Intellia Therapeutics — Technical Presentation (February 2022)
38 slides from Intellia Therapeutics's technical presentation, Feb 28, 2022
Slide 1: NTLA-2001 for ATTR Amyloidosis: Interim Clinical Results from Ongoing Phase 1 Trial
NTLA-2001 for ATTR Amyloidosis: Interim Clinical Results from Ongoing Phase 1 Trial Bill, living with transthyretin amyloidosis, and his wife, Maura February 28, 2022
Slide 2: Agenda
Agenda Welcome Introduction John Leonard, M.D. Chief Executive Officer, Intellia Therapeutics Review of NTLA-2001 Interim Phase 1 Clinical Trial Data Ed Gane, MBChB, MD, FRACP, MNZM Professor of Medicine, University of Auckland, New Zealand, Chief Hepatologist, Transplant Physician, Deputy Director,
Slide 3: 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 4: Agenda
Agenda Welcome Introduction John Leonard, M.D. Chief Executive Officer, Intellia Therapeutics Review of NTLA-2001 Interim Phase 1 Clinical Trial Data Ed Gane, MBChB, MD, FRACP, MNZM Professor of Medicine, University of Auckland, New Zealand, Chief Hepatologist, Transplant Physician, Deputy Director,
Slide 5: In Vivo Leader: First to Demonstrate Systemic CRISPR Gene Editing in Humans
In Vivo Leader: First to Demonstrate Systemic CRISPR Gene Editing in Humans “CRISPR injected into the blood treats a genetic disease for the first time” August 5, 2021 “CRISPR gene-editing ‘revolution’ treats internal organ for first time” “‘It’s a wow’: New CRISPR gene-editing success holds promise
Slide 6: Building a Full-Spectrum Genome Editing Company
Building 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 6
Slide 7: In Vivo Development Pipeline Fueled by Robust Research Engine
In Vivo Development Pipeline Fueled by Robust Research Engine IND- Early-Stage Late-Stage PROGRAM APPROACH Research PARTNER Enabling Clinical Clinical In Vivo: CRISPR is the therapy LEAD NTLA-2001: Transthyretin Amyloidosis Knockout * NTLA-2002: Hereditary Angioedema Knockout NTLA-2003: AATD-Liver D
Slide 8: Ex Vivo Development Pipeline Fueled by Robust Research Engine
Ex Vivo Development Pipeline Fueled by Robust Research Engine IND- Early-Stage Late-Stage PROGRAM APPROACH Research PARTNER Enabling Clinical Clinical Ex Vivo: CRISPR creates the therapy *** OTQ923 / HIX763: Sickle Cell Disease HSC NTLA-5001: Acute Myeloid Leukemia WT1-TCR NTLA-6001: CD30+ Lymphomas
Slide 9: Key Principles of Our Genome Editing Strategy
Key Principles of Our Genome Editing Strategy GENOME EDITING STRATEGY Precision editing Safety and specificity Consistency Durability 9
Slide 10: Ed Gane, MBChB, MD, FRACP, MNZM
Ed Gane, MBChB, MD, FRACP, MNZM Professor of Medicine, University of Auckland, Deputy Director NZ Liver Transplant Unit • Research interests: early phase development for new therapies for inherited and acquired liver diseases and liver cancer • Published over 600 articles in peer-reviewed journals i
Slide 11: Agenda
Agenda Welcome Introduction John Leonard, M.D. Chief Executive Officer, Intellia Therapeutics Review of NTLA-2001 Interim Phase 1 Clinical Trial Data Ed Gane, MBChB, MD, FRACP, MNZM Professor of Medicine, University of Auckland, New Zealand, Chief Hepatologist, Transplant Physician, Deputy Director,
Slide 12: In vivo CRISPR/Cas9 Editing of the TTR Gene by NTLA-2001: Interim Clinical Trial Results
In vivo CRISPR/Cas9 Editing of the TTR Gene by NTLA-2001 in Patients with Transthyretin Amyloidosis: Interim Clinical Trial Results Ed Gane, MBChB, MD, FRACP, MNZM New Zealand Clinical Research, Auckland, New Zealand University of Auckland, Auckland, New Zealand
Slide 13: Disclosures
Disclosures I disclose the following financial relationships with a commercial interest: • Member of scientific advisory boards: AbbVie, Aligos, AlloVir, Arbutus, Arrowhead, Assembly, Avalia, Clear B, Dicerna, DrugFarm, Gilead, GlaxoSmithKline, Invictus, Janssen, Merck, Novartis, Roche, Silverback,
Slide 14: Transthyretin (ATTR) amyloidosis
Transthyretin (ATTR) amyloidosis Rare, progressive, fatal disease • Caused by accumulation of amyloid deposits composed of misfolded transthyretin (TTR) protein • ATTR amyloidosis consists of two forms of the disease: hereditary and wild type • Rate of new diagnoses is increasing Hereditary ATTR amy
Slide 15: Potential for gene editing to address unmet need for ATTR amyloidosis
Potential for gene editing to address unmet need for ATTR amyloidosis • Therapy in ATTR amyloidosis is directed at reducing the circulating amyloid-forming protein – Gene silencing therapy knocks serum TTR down by ~80% and benefits neuropathy in ATTRv1 • Greater TTR knockdown is expected to achieve
Slide 16: NTLA-2001 is a novel, investigational CRISPR/Cas9-based in vivo gene editing therapy
NTLA-2001 is a novel, investigational CRISPR/Cas9-based in vivo gene editing therapy NTLA-2001 Complementary TTR sequence to sgRNA TTR gene Streptococcus pyogenes (Spy) Cas9 mRNA Lipid nanoparticle sgRNA; single guide RNA; TTR, transthyretin 16 This presentation includes data for an investigational
Slide 17: NTLA-2001 delivers sgRNA and Cas9 into the nucleus, which edit the TTR gene
NTLA-2001 delivers sgRNA and Cas9 into the nucleus, which precisely edit and inactivate the TTR gene 1. Cas9/sgRNA 2. Ribonucleoprotein induces 3. Endogenous DNA repair via ribonucleoprotein unwinding of chromosomal DNA, nonhomologous end joining results in enters nucleus then binds to DNA at TTR ge
Slide 18: In vitro: No detectable off-target editing with pharmacologic concentrations of sgRNA
In vitro: No detectable off-target editing with pharmacologic concentrations of sgRNA EC90 100 80 60 On target Editing frequency (%) Sequence 1 40 Sequence 2 Sequence 3 20 Sequence 4 Sequence 5 2.5 2.0 Sequence 6 1.5 Sequence 7 1.0 0.5 0 0.007 0.021 0.063 0.191 0.574 1.724 5.172 15.517 sgRNA concent
Slide 19: Non-human primates: Durable, >95% TTR reduction after single dose of NTLA-2001
Non-human primates: Durable, >95% TTR reduction after single dose of NTLA-2001 proportion of baseline, % (mean ± SD) 120 Control (n=3) 100 1.5 mg/kg (n=3) TTR protein production, 3.0 mg/kg (n=3) 80 6.0 mg/kg (n=3) 60 40 20 0 0 40 80 120 160 200 240 280 320 360 Day 19 This presentation includes data
Slide 20: Two-part phase 1 first-in-human study of NTLA-2001 in ATTRv-PN
Two-part phase 1 first-in-human study of NTLA-2001 in ATTRv-PN Today's interim data* presentation covers patients across all four dose levels Part I Part II Single-ascending dose Single-dose expansion cohort Population Adults with ATTRv 1.0 mg/kg† (n=6) with polyneuropathy 0.7 mg/kg (n=3) Administer
Slide 21: Patient demographics
Patient demographics Parameter 0.1 mg/kg 0.3 mg/kg 0.7 mg/kg 1.0 mg/kg All patients n=3 n=3 n=3 n=6 n=15 Age, years, 54 53 51 61 55 median (min, max) (50, 63) (46, 64) (19, 58) (49, 70) (19, 70) Sex, n (%) Male 1 (33%) 3 (100%) 2 (67%) 3 (50%) 9 (60%) Female 2 (67%) – 1 (33%) 3 (50%) 6 (40%) Self-re
Slide 22: Baseline characteristics
Baseline characteristics Parameter 0.1 mg/kg 0.3 mg/kg 0.7 mg/kg 1.0 mg/kg All patients n=3 n=3 n=3 n=6 n=15 TTR genotype, n (%) p.H110D 0 1 (33%) 0 0 1 (7%) p.S97Y 1 (33%) 1 (33%) 0 0 2 (13%) p.E94G 0 0 1 (33%) 0 1 (7%) p.T80A 2 (67%) 1 (33%) 1 (33%) 2 (33%) 6 (40%) p.S70R 0 0 0 1 (17%) 1 (7%) p.E6
Slide 23: NTLA-2001 was generally well tolerated across all dose levels
NTLA-2001 was generally well tolerated across all dose levels • Across all dose levels, the most frequent adverse events* were headache, infusion-related reactions, back pain, rash†, and nausea – Majority of adverse events were mild in severity with 73% (n=11) of patients reporting a maximal adverse
Slide 24: Majority of adverse events were mild in severity
Majority of adverse events were mild in severity 0.1 mg/kg 0.3 mg/kg 0.7 mg/kg 1 mg/kg All n=3 n=3 n=3 n=6 n=15 Parameter Gr. 1 Gr. 2 Gr. 3 Gr. 1 Gr. 2 Gr. 3 Gr. 1 Gr. 2 Gr. 3 Gr. 1 Gr. 2 Gr. 3 Gr. 1 Gr. 2 Gr. 3 Patients with at least one TEAE 3 – – 3 – – 2 – 1* 3 2 1† 11 2 2 Headache 2 – – – – – 2
Slide 25: Dose-dependent reductions in serum TTR, reaching a mean reduction of 93% at 1.0 mg/kg
Dose-dependent reductions in serum TTR, reaching a mean reduction of 93% at 1.0 mg/kg Mean (SE) % TTR reduction by dose level at Day 28 00 =–10 12 -10mo. –20 = -20 9 mo. –30 –40% -30 TTR reduction (%) (n=3) –40 -40 –52% (n=3) –50 -50 –60 -60 –70 -70 –87% –86% –80 -80 (n=3) (n=3) –93% –90 -90 (n=6) –
Slide 26: Consistent reductions in serum TTR at 1.0 mg/kg
Consistent reductions in serum TTR at 1.0 mg/kg Mean (SE) % TTR reduction by dose level at Day 28 0 00 =–10 12 -10mo. –65 –20 –70 = -20 9 mo. TTR reduction (%) –30 –40% -30 –75 TTR reduction (%) (n=3) –40 -40 –52% –80 (n=3) Percentage TTR –50 -50 –85 reduction for –60 -60 –90 each individual patient
Slide 27: Rapid reductions in serum TTR, achieving nadir by Day 28
Rapid reductions in serum TTR, achieving nadir by Day 28 Mean (SE) % TTR reduction by dose level through Month 2 0 0 0.1mg/kg 0.1 mg/kg(N (n=3*) = 3*) -10 –10 0.3 0.3mg/kg mg/kg(N = 3) (n=3) -20 –20 0.7 0.7mg/kg mg/kg(N = 3) (n=3) 1.0 1.0mg/kg mg/kg(N = 6†) (n=6 †) -30 –30 TTR reduction (%) -40 –40
Slide 28: Durable reductions in serum TTR were observed over the follow-up period
Durable reductions in serum TTR were observed over the follow-up period Mean (SE) % TTR reduction by dose level at Day 28 and at last follow-up 0 Day 28 –10 -10 Last follow-up visit –20 -20 –30 -30 Patient Dose TTR reduction (%) follow-up –41% –40 -40 0.1 mg/kg 9–12 months –52% –50 -50 0.3 mg/kg 9 m
Slide 29: First-in-human evidence of deep, consistent, and durable TTR reductions
First-in-human evidence of deep, consistent, and durable TTR reductions following in vivo CRISPR-based gene editing Single systemic administration of NTLA-2001 resulted in deep reductions in serum TTR 93% mean reduction 6 out of 6 patients at 1.0 mg/kg at 1.0 mg/kg by Day 28 achieved >80% reductions
Slide 30: Acknowledgments
Acknowledgments • We thank the patients who participated in this trial and their families • We thank our investigators: Jorg Taubel, Björn Pilebro, Julian Gillmore, Justin Kao, and Marianna Fontana • We acknowledge valuable input in the development of NTLA-2001 from Intellia Therapeutics and Regener
Slide 31: Agenda
Agenda Welcome Introduction John Leonard, M.D. Chief Executive Officer, Intellia Therapeutics Review of NTLA-2001 Interim Phase 1 Clinical Trial Data Ed Gane, MBChB, MD, FRACP, MNZM Professor of Medicine, University of Auckland, New Zealand, Chief Hepatologist, Transplant Physician, Deputy Director,
Slide 32: NTLA-2001 Expanded Phase 1 Study
NTLA-2001 Expanded Phase 1 Study Two-part, open-label, multi-center study in adults with hereditary ATTR with polyneuropathy (ATTRv-PN) or ATTR amyloidosis with cardiomyopathy (ATTR-CM) PART I PART II ATTRv-PN Single-Ascending Single Dose Intervention: patients Dose Escalation Expansion Cohort Singl
Slide 33: Next Steps for Advancing NTLA-2001 Clinical Evaluation
Next Steps for Advancing NTLA-2001 Clinical Evaluation NTLA-2001 ATTRv-PN o Selected fixed dose of 80 mg to be evaluated in Part 2, a single dose-expansion cohort, pending regulatory feedback o On track to initiate Part 2 in Q1 2022 NTLA-2001 ATTR-CM o Continue to enroll and dose patients in Part 1
Slide 34: Growing Confidence in NTLA-2001 as Potential Treatment for ATTR Amyloidosis
Growing Confidence in NTLA-2001 as Potential Treatment for ATTR Amyloidosis Supported by Key Insights from Ongoing Phase 1 Study Interim Data Generally well-tolerated at all dose levels Dose-response relationship with deep reductions at higher doses Consistent reductions in serum TTR across ATTRv-PN
Slide 35: Agenda
Agenda Welcome Introduction John Leonard, M.D. Chief Executive Officer, Intellia Therapeutics Review of NTLA-2001 Interim Phase 1 Clinical Trial Data Ed Gane, MBChB, MD, FRACP, MNZM Professor of Medicine, University of Auckland, New Zealand, Chief Hepatologist, Transplant Physician, Deputy Director,
Slide 36: Intellia is Opening a New Era of Medicine
Intellia is Opening a New Era of Medicine KEY TAKEAWAYS Growing body of evidence Plan to leverage modular Intellia is at the forefront NTLA-2001 could be a platform to advance a of genome editing and potential single-dose pipeline of CRISPR-based is the reference company treatment for ATTR investiga
Slide 37: Q&A NTLA-2001 Interim Phase 1 Clinical Data
Q&A NTLA-2001 Interim Phase 1 Clinical Data
Slide 38: Intellia Therapeutics
Inteizia THERAPEUTICS
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