Every day, more than 200 researchers and staff come to work at Intellia. We are motivated by our mission to develop curative genome editing treatments for people living with severe diseases.

Many of us pursuing work in the biotechnology industry are inspired by someone in our community who is living with a disease or the loss of a loved one. We know that rare and genetic diseases not only affect the people living with the often-debilitating and life-threatening symptoms, but also significantly impact their families, friends and caregivers.

Since the emergence of the breakthrough genome editing technology, CRISPR / Cas9, the science has moved fast in only a few years. Our researchers have worked tirelessly to harness this tool for human therapeutic use. We at Intellia are humbled to have a hand in making what I believe to be medical history. As a leader in this space, we take this responsibility to patients seriously, as we advance relentlessly toward clinical trials.

I invite you to learn more about this revolutionary technology and how Intellia intends to develop one-time curative treatments to transform lives.

John Leonard, M.D. President and Chief Executive OfficerIntellia Therapeutics

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Almost All Diseases Have a Genetic Component

THE HUMAN GENOMEThe complete set of human genes

FULLY MAPPED1 IN

2003

The Human Genome Project, started in 1990, paved the way for targeted gene editing. Completed in 2003, this mega project led to the identification of approximately 3 billion base pairs in the human genetic instruction set,4 which has given us the ability to seek out the genetic roots of disease while developing treatments.

A change in DNA sequence away from the normal sequence can cause a genetic disorder, according to the U.S. National Institutes of Health.

1 National Institutes of Health – National Human Genome Research Institute: https://www.genome.gov/For-Patients-and-Families/Genetic-Disorders

2National Institutes of Health – Genetics Home Reference: https://ghr.nlm.nih.gov/primer/testing/genepatents3Centers for Disease Control and Prevention: http://www.cdc.gov/nchs/FASTATS/lcod.htm4National Institutes of Health – Human Genome Project Fact Sheet: https://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=45

GENETIC DISORDERS2

4,300 9 of the 10

Scientists have identified the individual genes responsible for

many of which can drastically affect an individual’s quality of life or reduce life expectancy.

leading causes of death in the United States3

for example: chronic conditions like cancer, diabetes and heart disease.

Genomics play a role in

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Welcome to the CRISPR Revolution

Target Sequence

Guide Sequence

PAM

Cas9

tracrRNA + crRNAThe fundamental challenge is accessing and locating the site and intervening precisely at a location within 3 billion nucleotides of DNA

• Discovered as part of a bacterial defense system

• Developed for use in non-cellular and cellular settings, including human cells

• Mediated by a guide RNA targeting sequence and a catalytic protein known as “Cas9”

“The Biggest Biotechnology Discovery of the Century” – MIT Technology Review, 2014Seminal paper on the use of CRISPR-Cas9 to edit DNA published in 2012 by our co-founder. Dr. Jennifer Doudna, with Dr. Emmanuelle Charpentier catalyzed unprecedented research on the CRISPR / Cas9 technology!

More than 12,900 CRISPR-related scientific publications1

1 CRS analysis of data on scientific publications from Scopus (https://www.scopus.com) as of November 20, 2018

Harnessing a Natural Pathway

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Why Does CRISPR / Cas9 Have So Much Potential to be Used for Medicine?

• Potential one-time curative treatment

• Highly targeted − the ultimate personalized medicine

• Ability to target multiple DNA sites simultaneously

• Potential to work on monogenic or polygenic disorders*

CRISPR / Cas9

KNOCKOUT REPAIR INSERTInactivation / deletion of

disease-causing DNA sequence

*Monogenic disorders are caused by a mutation in one gene. Polygenic disorders are associated with mutations in more than one gene.

Correction of “misspelled” disease-driving DNA sequence

Insert new DNA sequence to manufacture therapeutic protein

TYPES OF EDITS USING CRISPR / CAS9 TO MODIFY THE GENOME

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Disruptive Innovation to Improve Health Care Outcomes for Patients with Genomic Diseases

Our Mission:Developing curative genome editing treatments that can positively transform the lives of people living with severe and life-threatening diseases.

How Intellia is Developing CRISPR / Cas9-Based Treatments

CRISPR / Cas9

Immuno-oncology Autoimmune diseases

Ex Vivo CRISPR / Cas9 Delivery

CRISPR creates the therapyModular Platform

LNP

Genetic diseases

In VivoCRISPR / Cas9 Delivery

CRISPR is the therapy

NTLA-2001 for Transthyretin

Amyloidosis

PH1 AATD

Genetic Diseases(targeting liver)

Genetic Diseases(targeting other tissues)

Acute Myeloid Leukemia

Immuno-Oncology Programs

Hematological Malignancies

Solid Tumors

PIPE

LIN

E

RNA

CELL

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Advancing Toward the Clinic

Our TimelineWe plan to submit our first Investigational New Drug (IND) application for Transthyretin Amyloidosis to the U.S. Food and Drug Administration (FDA) in mid-2020 to begin clinical trials.

Our MotivationConventional medicines treat the symptoms instead of the genetic cause of severe and life-threatening diseases, meaning that patients must take these therapies throughout their lives. We envision developing treatments that target the cause of diseases and can cure patients.

Our Goal Intellia is revolutionizing medicine by harnessing the power of genome editing. We are developing potential one-and-done curative genome editing therapies for people living with severe and life-threatening conditions, including cancers and genetic disorders.

Visit the U.S. National Institutes of Health website to learn how clinical trials work www.nih.gov/health-information/nih-clinical-research-trials-you/basics

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Driven to Develop Treatments with the Potential to Cure Serious Diseases

Want to Learn More?Check Out these CRISPR / Cas9 Resources

“ What are genome editing and CRISPR-Cas9?,” National Institutes of Health, Genetic Home Reference

www.ghr.nlm.nih.gov/primer/genomicresearch/genomeediting

“CRISPR Guide,” Addgene® www.addgene.org/crispr/guide/

Consensus Study: “Human Genome Editing: Science, Ethics, and Governance,” The National Academies of Sciences, Engineering, Medicine

www.nationalacademies.org/gene-editing/consensus-study/index.htm

Annual Report of the Chief Medical Officer 2016: “Generation Genome, United Kingdom Department of Health & Social Care”

www.gov.uk/government/publications/chief-medical-officer-annual-report-2016-generation-genome

“CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers”, National Institutes of Health, National Cancer Institute

www.cancer.gov/about-cancer/treatment/research/car-t-cells

ONE EXPLORE DISRUPT DELIVER

OUR VALUESOur values are at the heart of Intellia’s identity and culture.

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857-285-6200

40 Erie Street Cambridge, MA 02139

www.intelliatx.com