Company Presentation June 2016

Transcription

1 Company Presentation June 2016

2 Legal Disclaimers This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. All statements contained in this presentation other than statements of historical facts are forward-looking statements. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, target, should, would, and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements relate to the Company s strategy, intellectual property position, future operations, future financial position, potential revenue, projected costs, prospects, plans, objectives of management and expected market growth, and involve known and unknown risks, uncertainties and other factors that may cause the Company s actual results, levels of activity, performance or achievements to be materially different from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. The Company has based these forward-looking statements on management s current expectations, assumptions, estimates and projections. While the Company believes these expectations, assumptions, estimates and projections are reasonable, such forward-looking statements are only predictions and involve known and unknown risks, uncertainties and other important factors, many of which are beyond the Company s control and may cause actual results, performance or achievements to differ materially from those expressed or implied by any forward-looking statements. These risks and uncertainties include, without limitation, risks and uncertainties related to the initiation, timing, progress and results of the Company s research and development programs and future preclinical and clinical studies; the Company s ability to develop viable product candidates, achieve regulatory approval for any such product candidate, or market and sell any product candidates; the Company s ability to advance its therapeutic delivery capabilities; the timing or likelihood of regulatory filings and approvals; the timing or likelihood of any potential commercialization of the Company s product candidates, if approved; the pricing and reimbursement of the Company s product candidates, if approved; negative public opinion and increased regulatory scrutiny of gene editing therapies and the related effects on public perception and the Company s ability to obtain regulatory approval for its product candidates; the implementation of the Company s business model, including strategic plans for the Company s business, product candidates and technology; the scope of protection the Company is able to establish and maintain for intellectual property rights covering the Company s product candidates and technology; potential third-party claims of intellectual property infringement against the Company, its licensors or its collaborators; the Company s needs for additional financing; the Company s ability to establish, maintain and execute under strategic collaborations and other thirdparty arrangements; the Company s financial performance; and developments relating to the Company s competitors and the Company s industry. These and other risks and uncertainties are described in greater detail under Risk Factors section of the Company s Quarterly Report on Form 10-Q, which is on file with the U.S. Securities and Exchange Commission (SEC), and in other filings that the Company may make with the SEC in the future. The forward-looking statements in this presentation are made only as of the date hereof, and except as required by law, the Company undertakes no obligation to update any forwardlooking statements contained in this presentation as a result of new information, future events or otherwise. 2

3 Developing potentially curative gene editing treatments that can positively transform the lives of people living with severe and life-threatening diseases FOUNDERS PARTNERS 3

4 Company Overview Background Founded in May 2014 by Atlas Venture and CRISPR/Cas9 foundational thought leaders and KOLs Located in Cambridge, MA Licensed foundational IP portfolio (UC Berkeley) Experienced senior management team with proven drug discovery and development track records Key Events July 2014: IP license and research services agreement with Caribou Biosciences CRISPR company spun out from Dr. Doudna s lab December 2014: Novartis collaboration CAR T & HSC focus January 2016: Launch of extellia, focused on ex vivo opportunities April 2016: Regeneron collaboration focus on liver May 2016: $170M raised in IPO and private placements Priorities Accelerate development of potentially curative products Advance in vivo programs both proprietary and partnered with Regeneron Advance ex vivo pipeline both proprietary and partnered with Novartis Engage in further strategic alliances to expand pipeline, delivery tools and technology platform Maintain leading IP position 4

5 Leadership Team NESSAN BERMINGHAM, PHD Founder and Chief Executive Officer Venture Partner at Atlas Venture TOM BARNES, PHD Chief Scientific Officer VP of Discovery at Eleven Biotherapeutics JOHN LEONARD, MD Chief Medical Officer CSO at AbbVie DAVID MORRISSEY, PHD Chief Technology Officer Executive Director of RNAi at Novartis JOSÉ E. RIVERA Chief Operating and Legal Officer Division VP & Associate General Counsel, Intellectual Property Group at Abbott SAPNA SRIVASTAVA, PHD Chief Financial and Strategy Officer Senior Biotechnology Analyst at Goldman Sachs 5

6 CRISPR/Cas9 Technology & Opportunity

7 The CRISPR Revolution Led by Our Founders Seminal paper published by our co-founder and advisor, Dr. Jennifer Doudna, in 2012 Discovery catalyzed an unprecedented rate of research, with more than 2,600 research papers published Potential to revolutionize gene editing Ability to perform targeted, highly efficient alterations of genome sequence Knockout, repair or insert genes Potential to address polygenic or complex genetic disorders through multiplex editing Harnessing a natural pathway Discovered as part of a bacterial defense system; developed for use in human cells Mediated by a guide RNA targeting sequence and catalytic protein Cas9 New therapeutic class curative potential Ability to address previously undruggable targets Broader applicability to in vivo and ex vivo therapies Jennifer Doudna, Ph.D. Seminal paper recognizing broad utility for programmable gene editing Rodolphe Barrangou, Ph.D. Established CRISPR system function Luciano Marraffini, Ph.D. Clarified CRISPR/Cas9 mechanism Derrick Rossi, Ph.D. Pioneered use of CRISPR/Cas9 in stem cells Erik Sontheimer, Ph.D. Clarified CRISPR/Cas9 mechanism 7

8 CRISPR/Cas9 Delivers Precise Gene Editing and Can Address Disease at the Cellular Level CRISPR/Cas9: programmable molecular scissors Cas9 protein contains the scissors that cuts each strand of DNA Guide RNA targets the Cas9 protein cut; the guide RNA can be easily switched to target different sites Example: Example: Example: TTR (Amyloidosis) SERPINA1 (AATD) Many IEMs Error prone repair results in frame shift and loss of expression Correction of a single amino acid mutation Insertion of a large gene cassette Jiang et al Science 348:

9 CRISPR/Cas9 The Ideal Gene Editing Technology KEY ENABLING ATTRIBUTES High potency (cleavage efficiency) and specificity Broad applicability to both in vivo and ex vivo applications Simple editing tools (guide RNA plus protein) provide ability to scale and optimize at speed Potential one-time curative treatment BROADEST POTENTIAL TO MODULATE GENES Ability to target multiple DNA sites simultaneously Multifunctional programmability: knockout, repair or insert genes Multiplexing potential to address polygenic or complex genetic disorders 9

10 Leveraging Years of Progress to Accelerate CRISPR/Cas9 Therapeutic Potential GENE EDITING OMICS GENE AND CELL THERAPY Alignment of Scientific Progress DELIVERY 10

11 Our Approach

12 Our Approach: CRISPR/Cas9 and Gene Editing Risk Diversified With Ex Vivo and In Vivo Approaches EX VIVO IN VIVO CAR T oncology HSC Non CAR T oncology Autoimmune and inflammatory INITIAL FOCUS Liver Diseases (LNP Delivery) ADDITIONAL EXPLORATION Eye Muscle CNS 12

13 Our Approach: Potential to Unlock the Largest Opportunity in the Shortest Period of Time We see liver as the best organ to focus on initially Wide array of potential targets Potential to address multiple indications with high unmet medical need Existing delivery technology Proprietary lipid nanoparticles Strategy to rapidly leverage success in sentinel indications to multiple other liver targets Potential to rapidly accelerate clinical development through proprietary development and in partnership with Regeneron Risk diversify our pipeline by advancing ex vivo programs in parallel Initial ex vivo focus on CAR T and HSC programs using electroporation delivery extellia to help accelerate other ex vivo programs 13

14 In Vivo Therapeutic Development Strategy CRISPR/Cas9 Edit Knockout Repair Insertion Platform Progress Simple edits More complex edits Application Autosomal dominant disorders Infectious diseases Any genetic mutation Protein expression Insertion of wild-type protein Sentinel Liver Indications Transthyretin Amyloidosis Alpha-1 Antitrypsin Deficiency Hepatitis B Virus Inborn error of metabolism Alpha-1 Antitrypsin Deficiency Inborn errors of metabolism Inborn errors of metabolism 14

15 In Vivo Delivery: Lipid Nanoparticles (LNPs) Current focus on lipid nanoparticles (LNPs) CRISPR Components Delivered LNP / RNA Cas9 mrna + guide RNA LNP/ Ribonucleoprotein (RNP) Cas9 protein + guide RNA Cas9 Expression Transient Immunogenicity / Tolerability Biodegradable lipids improve clearance / tolerability Low immunogenicity Potential for re-dosing Tropism Current delivery to liver Opportunity to expand tropism to other organs Manufacturing Chemically well-defined and scalable 15

16 Our Pipeline of Sentinel Indications Programs Partnerships Type of Edit Delivery Upcoming Milestones In Vivo Transthyretin Amyloidosis (ATTR) Co-developing with Regeneron Knockout LNP to Liver Alpha-1 Antitrypsin Deficiency (AATD) Proprietary Knockout Repair LNP to Liver Hepatitis B Virus (HBV) Proprietary Knockout LNP to Liver Select 1 to 2 development candidates and advance to IND enabling studies in the next 12 to 24 months Inborn Errors of Metabolism (IEMs) Proprietary Knockout Repair Insertion LNP to Liver Ex Vivo Hematopoietic Stem Cells (HSCs) Selectively partnered with Novartis; proprietary Knockout Repair Insertion Electroporation First Novartis IND expected to be submitted in 2018 CAR T Cells Partnered with Novartis Knockout Insertion Electroporation Advance preclinical development 16

17 Transthyretin Amyloidosis (ATTR) Liver Program using Knockout Edit CLEAR UNMET MEDICAL NEED ATTR affects approximately 50,000 worldwide (various subtypes) Autosomal dominant; >120 known mutations Misfolded protein aggregates in nerves, heart, etc. leading to loss of function Onset ~20-70 yr; typically fatal within 2-15 yrs Standard of care is severely limited, symptomatic and largely ineffective Folded tetramer Folded monomer Aggregation-prone monomer OUR APPROACH Knock-down of disease causing protein is a clinically validated strategy Deletion of disease gene (mut TTR) in hepatocytes reduces supply of misfolded protein halts disease progression and may enable regression of tissue deposits Potential for curative treatment Co-developing with Regeneron Oligomers (pre-fibrillar) Amyloid fibril 17

18 Significant, Dose Dependent, In Vivo Editing of TTR Editing in Mouse Liver with Systemic Administration of LNPs In vitro editing In vivo editing In vivo serum TTR levels Mouse liver cells LNP directly administered to cells (n=3) Single administration in mice Median ± range (n=5) of cargo of cargo Assay for serum protein Median % of mean control ± range (n=5) 18

19 Ex Vivo Delivery: Electroporation Current focus on clinically validated electroporation Significant Bi-allelic Editing with Strong Cell Viability using Electroporation 60 85% bi-allelic editing % Bi-allelic KO Control Target 1 Target % viability Currently being used in advanced clinical studies % Viability Clinically viable for HSCs, T cells and additional ex vivo opportunities Control Target 1 24 h post electroporation Target 2 19

20 Therapeutically Relevant Multiplex Ex Vivo Editing Simultaneous delivery of Cas9 and guides targeting distinct genes Successful knockout of both targets with high efficiency No impact on viability or decreased individual bi-allelic editing efficiency Gene targeted Control Gene A Gene B Gene A+B Gene A Gene B 76% Gene A KO 80% Gene B KO 68% Gene A&B KO Guides are from different genes. CD3 + primary T cells. Electroporated RNP (n=3); one replicate shown 20

21 Significant Ex Vivo Opportunities Formed Extellia therapeutics, a fully owned division, to maximize ex vivo opportunity Novartis collaboration remains in Intellia extellia Opportunities Intellia/ Novartis Collaboration Immuno-oncology T-Cells (non-car T) & NK Cells Autoimmune and Inflammatory Diseases (AIID) CAR T HSC T regs Immuno-oncology opportunity Solid and liquid tumors TILs, CTLs, CAR-NK included AIID opportunity Focus on underserved autoimmune disorders Programs Undisclosed Programs Undisclosed Benefits Enhance efficacy via receptor engineering Enhance potency via checkpoint engineering Enhance safety via kill switches Simplify manufacturing allogeneic products, non-viral manufacturing Benefits Enhance efficacy via improved homing to target tissue Enhance potency via improved suppressor function 21

22 CRISPR/Cas9 Platform Capabilities Informatics & Guide Qualification Candidate guides are ranked based on editing activity Top guides are further ranked based on additional data behind every guide Guide Qualification Off Target Top guides are further ranked based on off-target activity Off-target assessment progresses through 3 steps Ranking of guides Identification of sites Utilization of sites RNA & Nuclease Formats Informatics Guide ranking using empirical method Top guides Unbiased OT method in cells Off-target activity ranking Off-target site identification List of sites OT 1 OT 2 OTn Off-target site utilization Targeted Next-Gen Seq in relevant cells Editing rates are affected by RNA and Cas9 formats Basic nuclease and RNA formats have been selected for both ex vivo and in vivo delivery RNA formats Frequency recovered Example data * * Intellia Guides No putative off-targets identified * One putative off-target site identified 22

23 Strategic Partnerships

24 Partnering Strategy Fundamental principles: Industry Leaders who share our vision Pioneers and/or leaders in a scientific and therapeutic field Commitment to accelerate development of life-saving therapeutics Focused Deal Structure Limited scope of collaboration Well-defined criteria which leverage key skills of both partners Access to strategic and financial assets Non dilutive financing Expertise and technology which complement and/or enhance our capabilities 24

25 Novartis Collaboration CAR T & HSC Editing Opportunities Collaboration Overview Product-focused discovery for CAR T and HSC products Access to proprietary LNP and HSC expansion technology Term: 5 year collaboration Financials: $10M upfront payment and equity investments $20M in technology access fees and up to $20M in research payments Up to $230.3M in milestone payments for the first two indications for each target Mid-single-digit royalties Programs HSC engineering opportunities First Novartis IND targeted for 2018 Correction of genetic disease Vehicle for systemic delivery of therapeutic proteins Access to Novartis HSC expansion technology CAR T engineering opportunities Enables universal donor concept Enhance effector function Improve delivery of CAR to the T-cell + 25

26 Regeneron Collaboration Advancing In Vivo Opportunities Product focused collaboration to research, develop and commercialize therapies primarily focused on gene editing in the liver Regeneron may obtain exclusive rights for up to 10 targets May select up to 5 targets in non-liver organs subject to certain conditions Technology collaboration to advance CRISPR/Cas platform Six-year term, with potential for two year extension Financials: $75M upfront payment $50M in equity investment Collaboration Overview Up to $320M in milestone payments per licensed target High single to low teen royalties (net royalties in single digits) 26

27 Regeneron Collaboration Advancing In Vivo Opportunities Programs and Strategic Considerations Intellia and Regeneron will co-develop and co-commercialize ATTR ATTR is Regeneron s first selected target Intellia is the lead party for the co-development / co-commercialization Other sentinel indications (HBV, AATD and select IEMs) remain exclusive to Intellia Intellia has co-development and co-commercialization options on future Regeneron-selected targets Regeneron has additional options on Intellia s future liver targets Access to the Regeneron Genetics Center and mouse models: Potential to accelerate and enhance preclinical development 27

28 Financial Foundation

29 Strong Financial Foundation $255M in equity capital raised since inception More than $125M in committed collaboration funding Novartis: Up to $50M total commitment in upfront, tech access and R&D payments ($19M received to-date); in addition to milestones and royalties Regeneron: $75M total upfront commitment, in addition to milestones and royalties Cash runway through at least mid

30 IP Portfolio & Foundation

31 Leading Intellectual Property Position INTELLIA DEVELOPED OR OTHER IP LNP and HSC-expansion technology; future IP from collaboration Current and future CRISPR/Cas9- related IP for human therapeutics Collaboration IP CARIBOU DEVELOPED IP DOUDNA/CHARPENTIER IP [co-owned by UC Berkeley, U Vienna, Charpentier] OTHER IN-LICENSED IP [Pioneer (DuPont) & Wageningen] 31

32 Looking Ahead

33 Upcoming Milestones Programs Partnerships Type of Edit Delivery Upcoming Milestones In Vivo Transthyretin Amyloidosis (ATTR) Co-developing with Regeneron Knockout LNP to Liver Alpha-1 Antitrypsin Deficiency (AATD) Proprietary Knockout Repair LNP to Liver Hepatitis B Virus (HBV) Proprietary Knockout LNP to Liver Select 1 to 2 development candidates and advance to IND enabling studies in the next 12 to 24 months Inborn Errors of Metabolism (IEMs) Proprietary Knockout Repair Insertion LNP to Liver Ex Vivo Hematopoietic Stem Cells (HSCs) Selectively partnered with Novartis; proprietary Knockout Repair Insertion Electroporation First Novartis IND expected to be submitted in 2018 CAR T Cells Partnered with Novartis Knockout Insertion Electroporation Advance preclinical development Corporate Goals: Establish additional strategic alliances with leading pharmaceutical and biotechnology partners Continue to strengthen IP position 33

34 Intellia s Strong Foundation Positions for Success and Long-Term Growth FOUNDERS PARTNERS 34

35