Wedbush PacGrow Healthcare Conference August 15, 2018

Transcription

1 Wedbush PacGrow Healthcare Conference August 15,

2 Disclaimer This presentation has been prepared by AVROBIO, Inc. ( AVROBIO ) for informational purposes only and not for any other purpose. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on studies, publications, surveys and other data obtained from third-party sources and AVROBIO s own internal estimates and research. While AVROBIO believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. While AVROBIO believes its internal research is reliable, such research has not been verified by any independent source. This presentation may contain trade names, trademarks or service marks of other companies. Forward Looking Statements: This presentation may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of Such forward-looking statements are based on our current expectations, estimates and projections about our industry as well as management's beliefs and assumptions. Words such as anticipates, expects, intends, plans, believes, seeks, estimates, may, will, and variations of these words or similar expressions are intended to identify forward-looking statements. These statements include statements regarding our business strategy, prospective products, clinical trial results, product approvals and regulatory pathways, timing and likelihood of success, plans and objectives of management for future operations, future results of anticipated products, and the market opportunity for our product candidates, and speak only as of the date hereof. Such statements are based upon the information available to us now and are subject to change. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict and that could cause actual results to differ materially and adversely from those expressed in any forward-looking statements. These risks and uncertainties include, but are not limited to, the factors discussed in the Risk Factors section of our Quarterly Report on Form 10- Q for the quarter ended June 30, 2018, as well as other risks detailed in our subsequent filings with the Securities and Exchange Commission. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of new information, future events, changed circumstances or otherwise. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. No representations or warranties (express or implied) are made about the accuracy of any such forward-looking statements. 2

3 Curing rare disease in a single dose. Just as enzyme replacement therapies (ERTs) revolutionized the past, gene therapy has the potential to revolutionize the future. 3

4 Clinical-Stage Company Developing Disruptive Gene Therapies to Cure Rare Diseases Developing first-line therapies for lysosomal storage diseases (LSDs) Initial programs in Fabry, Gaucher, Pompe and cystinosis Compelling Fabry preliminary Phase 1 data and Phase 2 trial initiated Targeting standard of care therapies with ~$4B ww 2017 net sales Expanding lentiviral-based gene therapy via mild conditioning Establishing robust manufacturing solutions to support global strategy World class management team and investors 4

5 Cell, Gene and Rare Disease Industry Leaders Experienced Management Team Board of Directors Geoff MacKay President and CEO, Director Katina Dorton, MBA, JD Chief Financial Officer Bruce Booth, DPhil Chairman Ian Clark Kim Warren, PhD Head of Operations Nerissa Kreher, MD, MS, MBA Chief Medical Officer Annalisa Jenkins, MBBS, FRCP Chris Mason, MD, PhD, FRCS Chief Science Officer Kathryn McNaughton, PhD SVP Portfolio & Program Management Phillip Donenberg Chris Paige, PhD Deanna Petersen, MBA Chief Business Officer Scott Requadt, JD, MBA Joshua Resnick, MD, MBA CORMORANT ASSET MANAGEMENT 5

6 Proven Platform, Proven Disease Targets Enzyme Replacement Therapy (ERT) 1973 First ERT in patients with Gaucher 1991 FDA approval of ERT for Gaucher 2003 FDA approvals of ERTs for Fabry and MPS 2006 FDA approval of ERT for Pompe LSDs have well-understood biology ERT validates exogenous enzyme delivery Established regulatory and reimbursement processes ERTs emerge GT validated Proven lentiviral gene therapy platform 1990 World s first gene therapy administered 2003 First clinical trials with lentiviral gene therapy 2016 EMA approval of Strimvelis, displaces ERT for ADA-SCID Transformative pivotal outcomes from Bluebird and GSK for lentiviral ex vivo gene therapies 2017 FDA approval of Luxterna for RPE65 retinal dystrophy >200 patients treated in rare disease clinical trials 10+ years of promising efficacy and safety Gene Therapy 6

7 One Optimized Platform Applied Across Our Portfolio Transduce with lentiviral vector carrying normal gene Select CD34+ stem cells Harvest and freeze 1 Collect mobilized blood 5 Infuse Gene Therapy Platform 7

8 Mild Conditioning Supports First-Line Therapy Improved Patient Tolerability via Minimal Intensity Conditioning Approach Toxicity and number of hospital days Myeloablative Reduced intensity / non-ablative Minimal Intensity Conditioning Potential number of patients 8

9 Lentiviral Gene Therapy Enables Durable, Systemic Delivery of Proteins Long-Term Engraftment in Bone Marrow Manufacturing, Transportation and Delivery in Blood Final Destination in Tissues and Organs T NK Enzyme released B RBC Platelets Granulocytes DC Monocytes Enzyme released DC Macrophages More enzyme released 9

10 Plasma Pharmacokinetics of ERT Functional Protein Expression in Transduced HSCs and Their Progeny Life-Long Treatments vs. Single Dose Potential Cure Disease Progression Continues Enzyme Replacement Therapy (ERT) Temporary bolus of enzyme, not curative Disease Progression Can Halt AVROBIO Gene Therapy 24/7 expression of protein, curative potential 24/7 expression Life-long infusions Enzyme or protein level Bi-Weekly ERT Transient, intermittent elevation One-Time Gene Therapy Long-term, continuous elevation Treatment burden Bi-weekly IV infusions Single IV infusion 10

11 Steady Stream of Clinical-Stage Products Program Proof-of- Concept IND- Enabling Phase 1 Phase 2 Pivotal Expected Next Milestone Worldwide Rights Fabry AVR-RD-01 First Phase 2 patient data AVROBIO Gaucher AVR-RD-02 Initiate Phase 1/2 clinical trial AVROBIO Pompe AVR-RD-03 Advance preclinical program AVROBIO Cystinosis AVR-RD-04 Academic partner file IND AVROBIO 11

12 Plasma AGA activity (nmol/hr/ml) Significant Enzyme Activity Elevation After Single Dose Level of AGA Enzyme Activity Rose from Nearly Undetectable Levels to Levels Above the Range for Males with Classic Fabry Disease Non-Fabry Male Birth Day 0 Day 30 2 Months 3 Months 6 Months 9 Months 12 Months Infuse AVR-RD-01 Classic Male Fabry Patient 1 Patient 2 Bone marrow aspirate data at 14 months continues to support engraftment with a colony forming assay result of 13% VCN Patient 1 Patient 2 Drug Product Month Month Month 0.35 n/a 9 Month 0.26 n/a 12 Month 0.16 n/a Source: Tsukimura T et al, Mol Genet Metab, 2014 Note: Enzyme measurements are taken at ERT troughs 12

13 Neutrophils (X 10 9 /L) Platelets (X 10 9 /L) Mild Conditioning to Develop First-Line Therapies Neutrophil Count Recovered Rapidly Platelet Count Recovered Rapidly Patient 1 Patient 2 90 day result for Patient 1 is day result for Patient 1 is Day 0 Day Day Day 0 Day Day 0 16 Melphalan 100mg/m 2 IV on Day-1 Note: Neutrophil count lower range defined as when patients no longer require GCSF support per OZM-074 protocol Note: Platelet count lower range defined as when platelet transfusion support would be considered clinically given increased risk of spontaneous bleeding 13

14 AVROBIO-Sponsored Phase 2 Fabry Trial First Patient Dosed June 7 Open-Label, Multinational Study of the Efficacy and Safety of Ex Vivo Lentiviral-Based Vector Gene Therapy AVR-RD-01 for Treatment-Naïve Subjects with Classic Fabry Disease Objectives Patients Assess Efficacy (biomarkers and functional endpoints) Safety 8-12 patients Adult males (age 16 years) Treatment-naïve Substrate reduction (Gb 3 and/or lyso-gb3) in urine, plasma, skin, kidney Enzyme (AGA) activity Kidney function Cardiac size GI symptoms Pain and quality of life Vector Copy Number (VCN) and chimerism Safety 14

15 Glucocerebrosidase (GCase) Activity (nmol/mg protein/hr) Glucocerebroside (nmol/mg protein) Compelling Pre-Clinical Gaucher Data AVR-RD-02 Leads to Significant Elevation of GCase Activity Across Multiple Clinically Relevant Tissues AVR-RD-02 Leads to Significant Reduction in Glucocerebroside Levels Across Multiple Clinically Relevant Tissues p<0.05 p< p< p<0.01 p<0.001 p<0.01 Bone Marrow Spleen Liver Bone Marrow Spleen Liver Normal mice Untreated Gaucher mice Gaucher mice post AVR-RD-02 Source: Dahl M et al, Mol Ther,

16 Spleen Relative to Body Weight (mg/g) Compelling Pre-Clinical Gaucher Data Ex Vivo Lentiviral-Based Gene Therapy Leads to Significant Reduction in Spleen Volume in a Mouse Model of Gaucher Disease p<0.01 Normal mice Untreated Gaucher mice Gaucher mice post AVR-RD-02 Source: Dahl M et al, Mol Ther,

17 Planned AVROBIO-Sponsored Phase 1/2 Gaucher Trial - CTA Filing H Open-Label, Multinational Study of the Efficacy and Safety of Ex Vivo Lentiviral-Based Vectormediated Gene Therapy AVR-RD-02 for Subjects with Type 1 Gaucher Disease Objectives Patients Assess Efficacy (biomarkers and functional endpoints) Safety 8-16 patients Males and females ( 16 years, 35 years of age) Both switch-stable and treatmentnaïve Hemoglobin concentration Platelet count Liver volume Spleen volume Vector Copy Number (VCN) and chimerism GCase activity Bone mineral density Biomarkers (e.g. chitotriosidase, CCL18, BMB) Quality of life Safety 17

18 Pompe Disease Requires a More Potent Approach The Challenge Pompe requires 20x more ERT than Fabry or Gaucher GILT-Tag Version of Recombinant Human (rh)gaa Impact on Levels of Stored Glycogen Compared to Non GILT-Tagged Recombinant Human (rh)gaa Distribution of enzyme into muscle is limited The Solution AVROBIO s gene therapy platform combined with a patented GILT tag to create a fusion protein GILT tag increases lysosomal uptake of enzyme in muscle 25x Clinical proof-of-concept with GILT-rhGAA demonstrated by BioMarin rhgaa GILT-rhGAA rhgaa GILT-rhGAA Source: Maga JA et al, J of Bio Chem

19 Cystine Content Level (nmol half cystine/mg protein) Cystinosis is a Serious Rare Genetic Disease Disease Mutations in the CTNS gene resulting in deficiency in a lysosomal exporter protein, cystinosin Leads to accumulation of cystine in tissues and organs Impact Premature mortality Renal Fanconi syndrome, kidney failure requiring transplant, corneal cysteine crystals, visual impairment, myopathy, hypothyroidism, rickets Transplantation of Allogeneic Hematopoietic Stems Cells Results in Reduction of Cystine Crystals in Corneas of Cystinosis Mice AVR-RD-04 Leads to Lower Cystine Levels in Multiple Tissues in a Mouse Model of Cystinosis p<0.05 Standard of Care Cysteamine Not curative, relentless progression of disease continues Burdensome and expensive p<0.05 p<0.05 Population Estimates 1:170,000 live births Liver Spleen Kidney (male only) Untreated Cystinosis mice Cystinosis mice post AVR-RD-04 Sources: Gahl et al, NEJM, 2002; Bois et al, J Med Genet, 1976 Harrison F et al, Mol Ther, 2013; Rocca C et al, J Invest Ophthalmol Vis Sci,

20 Regulatory Strategy Drives Speed-to-Market Global Solutions to Accelerate Every Step of Development 1. Speed to Start Trials 2. Speed to Recruit Trials 3. Speed to Market Initiate phase 1/2 studies in countries with most efficient CTA approvals Canada Australia Leverage Fabry clinical trial approvals for fast Gaucher start Planned patient enrollment via clinical trials across 4 continents Canada Australia USA (2019) Japan (2019) EU (2019) Israel (2019) Navigate accelerated approval pathways FDA Draft Guidelines for Cell & Gene Therapy FDA Regenerative Medicine Advanced Therapies (RMAT) EMA Priority Medicines (PRIME) PMDA Conditional Time- Based Approval for Cell & Gene Therapy 20

21 Global Manufacturing Solutions in Place Infrastructure Ready to Run Global Clinical Programs Plasmid CMOs Vector CMOs Completed GMP-source plasmid production for 3 common plasmids and 3 transgene plasmids (Fabry, Gaucher and cystinosis) Discussions initiated for research plasmids (Pompe) Completed GMP production for Fabry, Gaucher and cystinosis 2 nd source vendor in place Discussions initiated for vector development Drug Product CMOs GMP-ready GMP-ready Process development of Prodigy and optimized vector GMPreadiness in progress for Fabry Process development of Prodigy and optimized vector GMPreadiness in progress for Gaucher Additional global sites under evaluation 21

22 Industry-Leading Technology Platform Cells Production time 3 days 3 days 3 days Closed system No PD* Yes Automated platform Potent, Scalable, Cost-Effective No PD Yes Cryopreserved Yes Yes 3 of 4 Vector Plasmid system 3 plasmid 4 plasmid 4 plasmid Enhanced Uptake Scalable serum-free suspension process Transduction efficiency No Yes 50 liter Yes 50 liter 25%-40% 50%-60% 60%+ Drug Product VCN Stable producer cell line No R&D R&D GILT tag No R&D PD * PD = Process Development 22

23 AGA Enzyme Activity (Day 4 nmoles/hr/ml) VCN (Day 4) GCase Enzyme Activity (Day 4 nmoles/hr/mg) VCN (Day 4) Next Generation Vectors Outperform First Generation LV2 v. LV1 Fabry Performance LV2 v. LV1 Gaucher Performance LV2_AGA LV1_AGA LV2_VCN LV1_VCN LV2_GBA LV1_GBA LV2_VCN LV1_VCN MOI 0 MOI 10 MOI 20 MOI 50 MOI MOI 0 MOI 10 MOI 20 MOI 50 MOI Multiplicity of Infection (MOI) Multiplicity of Infection (MOI) 23

24 Addressing Multi-Billion Dollar Markets Current Standard of Care Costs Disease Est. Cost Per Year Approx Net Sales Fabry $320K $1.4B Gaucher $ K $1.4B Pompe $500K $1B Cystinosis $ K n/a Single-dose AVROBIO Gene Therapy Sources: Rombach S et al, Orphanet J Rare Dis, 2013; van Dussen L et al, Orphanet J Rare Dis, 2014; WAC pricing from Redbook; 2017 Net Sales from company annual reports 24

25 Well Capitalized via Strong Investor Base Capital Raised IPO (June 2018) $114.7M Series B $60.5M (co-led) CORMORANT ASSET MANAGEMENT Series A $25M Seed $1.5M Cash Available (as of 6/30/18) Approx. $155M Credit Facility - Silicon Valley Bank $10M facility, not drawn down to-date 25

26 Steady Stream of Important Data and Milestones Post-IPO 2Q H H H 2019 Patient 1 12-month data 18-month data 24-month data Fabry (AVR-RD-01) IST* Patient 2 Patient 3 3-month data 6-month data 12-month data 6-month data Ongoing clinical data points and continued patient enrollment AVRO Patient 1 Dosed in June 6-month data Gaucher (AVR-RD-02) AVRO CTA Filing Initiate Phase 1/2 trial in 2019 Pompe (AVR-RD-03) AVRO Advance preclinical program Cystinosis (AVR-RD-04) IST Initiate Phase 1/2 trial in 2019 * IST = Investigator-Sponsored Trial 26

27 Potential to cure rare diseases in a single dose Phase 2 trial in Fabry disease initiated Broad pipeline of first-in-class clinical-stage assets Targeting diseases with ~$4B ww 2017 net sales 27