Slide 1: Phase 3 HAELO Clinical Trial: Topline Data for Lonvo-z
Phase 3 HAELO Clinical Trial: Topline Data for Lonvo-z April 27, 2026
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: Today's Speakers
Today’s Speakers Dr. John Leonard, President and Chief Executive Officer Intellia Therapeutics Dr. David Lebwohl, Executive Vice President and Chief Medical Officer Intellia Therapeutics Dr. Marc Riedl, Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Ang
Slide 4: Introduction
Introduction Dr. John Leonard President & CEO, Intellia Therapeutics
Slide 5: CRISPR is Coming of Age
CRISPR is Coming of Age 2020 1987 2012 Nobel Prize in Chemistry 2023 Discovery of natural CRISPR/Cas9 awarded to Intellia co-founder FDA approval of first ex vivo CRISPR systems in 2 publication in Science Jennifer Doudna CRISPR-based therapy E. coli bacteria1 2014 Intellia Therapeutics founded
Slide 6: Intellia's Mission Statement
Intellia’s Mission Statement To transform the lives of people with severe diseases by developing and commercializing potentially curative treatments.
Slide 7: CRISPR is Coming of Age
CRISPR is Coming of Age 2020 1987 2012 Nobel Prize in Chemistry 2023 Discovery of natural CRISPR/Cas9 awarded to Intellia co-founder FDA approval of first ex vivo CRISPR systems in 2 publication in Science Jennifer Doudna CRISPR-based therapy E. coli bacteria1 2024-2025 2020 Intellia doses first TOD
Slide 8: Intellia's Pipeline Advancing Toward Significant Near-Term Milestones
Intellia’s Pipeline Advancing Toward Significant Near-Term Milestones Research/ Early-Stage Late-Stage BLA Prog ram Indication Preclinical Clinical Clinical Submission Lonvo-z1 Hereditary Angioedema (HAE) Transthyretin Amyloidosis with LEAD Polyneuropathy (ATTRv-PN) Nex-z2 Transthyretin Amyloidosis
Slide 9: About HAE and Lonvo-z
About HAE and Lonvo-z Dr. David Lebwohl Chief Medical Officer, Intellia Therapeutics
Slide 10: Hereditary Angioedema (HAE): Currently a Lifelong Condition with Significant Burden
Hereditary Angioedema (HAE): Currently a Lifelong Condition with Significant Burden Rare, genetic and life-threatening disease • Caused by a hereditary deficiency or dysfunction of the C1 inhibitor protein that leads to an imbalance in the kallikrein-kinin system and an overproduction of bradykinin
Slide 11: Despite Available Treatments, Many Patients are Unable to Break the Chronic Cycle
Despite Available Treatments, Many Patients are Unable to Break the Chronic Cycle of Managing Their HAE Patient-Reported Burdens Lifelong Incomplete Significant Treatment for Control for Most Financial Impact All Life-Threatening Burden to Attacks Maintain Access 80% reported having 68% highly 45% h
Slide 12: The Cumulative Costs for Chronic HAE Treatments are Sizable
The Cumulative Costs for Chronic HAE Treatments are Sizable U.S. Treated Patients Average Age of HAE Cumulative U.S. Healthcare System Costs for with Type 1 & 2 HAE1 Diagnosis in U.S.2 Chronic and On-Demand HAE Therapies3 ~7,000 $19.1B On Demand LTP ~2,600 On Demand ~20 $11.5B ~4,400 LTP $3.8B $9 $3
Slide 13: Lonvo-z is an Investigational One-Time HAE Treatment Intended to Permanently Inactivate KLKB1
Lonvo-z is an Investigational One-Time HAE Treatment Intended to Permanently Inactivate the KLKB1 Gene In HAE, C1 inhibitor deficiency imbalances the Lonvo-z was designed to stop HAE attacks: kallikrein-kinin system (KKS), leading to excess Inactivating KLKB1 gene resets the KKS to stop protein prod
Slide 14: Lonvo-z is Designed to be Administered in an Outpatient Setting
Lonvo-z is Designed to be Administered in an Outpatient Setting in Two to Four Hours DAY PRIOR DAY OF One dose of orally One dose of each of Single outpatient infusion† Return home administered steroid the following: steroid, (at home)* histamine blocker, STP* gene the gene the editing and Targeting
Slide 15: Pooled Analysis of Phase 1/2 Clinical Data
Pooled Analysis of Phase 1/2 Clinical Data: After Becoming Attack-Free and LTP-Free for ?6 Months, All Patients Maintained Their Response Patient ID* Baseline Monthly LTP initiation LTP withdrawal Attack-free and LTP-free: ?6 months <6 months Attack: Mild Moderate Severe Phase-Initial Dose-Pt # Atta
Slide 16: No Waning of Effect Observed: Kallikrein Reduction Deep and Durable
No Waning of Effect Observed: Kallikrein Reduction has Remained Deep and Durable Pooled Data from All 32 Patients Who Received 50 mg Dose of Lonvo-z in Phase 1/2 0% -10% -20% kallikrein SD) ± -30% (mean -40% plasma in -50% baseline -60% change from -70% -86% -87% Percent -80% -89% -89% -90% -100% BL
Slide 17: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator
Slide 18: A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z
A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z as a One-Time HAE Treatment End of Study Day 1 Week 28 Week 104 Lonvo-z 50 mg Placebo (n=52) All patients Efficacy invited to Screening 1 Screening 2 One-time infusion evaluation Optional, Follow-up enroll in the LTP washout Run
Slide 19: Phase 3 Trial Design of Lonvo-z as a One-Time HAE Treatment
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 20: Trial Achieved its Primary and All Key Secondary Endpoints
HAELO Trial Achieved its Primary and All Key Secondary Endpoints Mean Attack-Rate Reduction Weeks 5—28 Attack Free Weeks 5—28 (Primary Endpoint) 1,2 (Key Secondary Endpoint) 2 2.5 70% 2.10 62% 60% 2 50% 1.5 87% reduction patients of 40% Odds Ratio 12.8 attacks/month (95% CI: 78%-93%) E 1 p<0.0001 30
Slide 21: 100% of Patients in Lonvo-z Arm Experienced Attack-Rate Reductions
100% of Patients in Lonvo-z Arm Experienced Attack-Rate Reductions from Baseline During Weeks 5-28 Clinically relevant Attack-free and 62% 38% 72% mean attack-rate therapy-free reduction* All patients who received lonvo-z at baseline or in crossover were LTP-free
Slide 22: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 23: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 24: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 25: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 26: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 27: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 28: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 29: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 30: Phase 3 Clinical Data
HAELO Phase 3 Clinical Data Dr. Marc Riedl Professor of Medicine, Clinical Director of the U.S. Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California San Diego; HAELO principal investigator A Placebo-Controlled, Double-Blind, Randomized Phase 3 Trial of Lonvo-z a
Slide 31: Q&A
Q&A
Slide 32: Intellia Therapeutics
Intellia therapeutics