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Freedom from a lifetime of disease
Corporate Presentation January 2020 Exhibit 99.1
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 AVROBIO 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 forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and
phrases such as "aims," "anticipates," "believes," "could," "designed to," "estimates," "expects," "forecasts", "goal,"
"intends," "may" "plans," "possible," "potential," "seeks," "will," and variations of these words and phrases or similar expressions that are intended to identify
forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy, prospective products and goals, the therapeutic potential of our investigational gene therapies, the design,
commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, potential regulatory approvals and the timing thereof, anticipated benefits of our gene therapy platform
including potential impact on our commercialization activities, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, the expected safety profile of our investigational gene
therapies, timing and likelihood of success, plans and objectives of management for future operations, future results of anticipated products, and the market opportunity for and anticipated commercial activities relating to our investigational gene
therapies, and statements regarding the Company's financial and cash position and expected cash reserves. Any such statements in this presentation that are not statements of historical fact may be deemed to be forward-looking statements. Any
forward-looking statements in this presentation are based on AVROBIO's current expectations, estimates and projections about our industry as well as management's current beliefs and expectations of future events only as of today and are
subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to,
the risk that any one or more of AVROBIO's investigational gene therapies will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators or of
encountering challenges in the enrollment or dosing in such clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, the risk that our investigational gene therapies or procedures in connection with
the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be
replicated or will not continue in ongoing or future studies or trials involving AVROBIO's investigational gene therapies, the risk that we will be unable to obtain and maintain regulatory approvals for our investigational gene therapies, the
risk that the size and growth potential of the market for our investigational gene therapies will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our
estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, and risks relating to our ability to obtain and maintain intellectual property protection for our investigational gene
therapies. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIO's actual results to differ from those contained in the forward-looking statements, see the section entitled
"Risk Factors" in AVROBIO's most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in AVROBIO's subsequent filings with the Securities and Exchange
Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Note regarding trademarks: plato is a trademark of AVROBIO. Other trademarks referenced in this presentation are
the property of their respective owners.
Just as enzyme replacement therapies
(ERTs) revolutionized the past, gene therapy has the potential to revolutionize the future. 'S MISSION: To cure rare disease in a single dose
Reported initial data, including 87%
substrate reduction in first kidney biopsy 9 patients dosed to date Continue to report data, including initial platoTM patient data Gain clarity on potential regulatory approval pathway 2019 Accomplishments entered 2019 with one program in
clinic generating data across 3 clinical programs in 2020 IND: Investigational New Drug 2020 Anticipated Milestones GAUCHER CYSTINOSIS POMPE FABRY First patient dosed Rolled out platoTM platform Dosed first patient under platoTM platform
Initiated patient recruitment Expanded management team Strengthened balance sheet with $138 million follow-on offering Report initial patient data Report initial patient data Complete pre-clinical IND-enabling activities Dose patients across Fabry
and Gaucher trials under platoTM platform Manufacture on 3 continents Hold first AVROBIO "R&D Day" Initiated pre-clinical IND-enabling study Building value across pipeline and platform
Steady stream of clinical programs
Investigational Gene Therapy Proof-of-Concept IND-Enabling Phase 1/2 Commercial Rights Fabry AVR-RD-01 AVROBIO Gaucher AVR-RD-02 AVROBIO Cystinosis AVR-RD-04 AVROBIO Pompe AVR-RD-03 AVROBIO 10 patients dosed; 3 programs actively recruiting
Addressing multi-billion dollar markets
Disease Est. Cost Per Patient Per Year Approx. 2018 Net Sales Selected Companies Fabry $1.4B Gaucher $1.4B Pompe $1B Cystinosis $0.2B CURRENT STANDARD OF CARE COSTS Sources: Rombach S et al, Orphanet J Rare Dis, 2013; van Dussen L et al, Orphanet J
Rare Dis, 2014; WAC pricing from Redbook; 2018 Net Sales from company annual and other reports *= for Horizon's Procysbi oral therapy (delayed release cysteamine bitartrate) Note: Shire acquired by Takeda in 2019 $320k $250k-400k $500k
One approach applied across our
portfolio Transduce with lentiviral vector carrying normal gene GENE THERAPY APPROACH Select CD34+ stem cells Collect mobilized blood 3 2 1 Harvest and freeze 4 Infuse 5
AVROBIO's foundation for worldwide commercialization Beginning-to-end manufacturing platform Redefines manufacturing best practices Optimized for performance
platoTM designed to durably express
functional protein throughout the body and brain BONE MARROW Potential for widespread microglia engraftment throughout the brain MICROGLIA PERIPHERAL TISSUE Mature Blood Cells Enzyme Neuron Microglia Enzyme Astrocyte Lymphocyte Granulocyte
Bloodstream Monocyte Enzyme Macrophage Mature cells area Progenitors area HSC area Bone TRANSDUCED CD34+ CELLS Viscera CNS/PNS IN THE BONE MARROW Busulfan eliminates hematopoietic (CD34+) stem cells making space for gene-modified cells BRAIN
Busulfan crosses blood-brain barrier and eliminates resident microglia cells making space for gene-modified cells
platoTM designed to deliver
differentiated, cost-effective approach to large-scale gene therapy manufacturing Drug product production Scalable, global production suites Frozen in aliquots to streamline supply chain CD 34+ hematopoietic stem cells Vector production Large
bioreactor 200 liter serum-free suspension culture Automated, closed system Vector with disease-specific transgene OPTIMIZE STEM CELL QUALITY HIGH VOLUME / TITRE 1 2 3 COST-EFFECTIVE SCALE-OUT Cryopreserved to enable convenient dosing Illustrative *
European manufacturing capabilities planned for 2H 2020; manufacturing capabilities currently in place in U.S. & Australia *
DRUG PRODUCT Poised to manufacture
at commercial scale VECTOR (200 L scale bioreactor runs (109 titre)) 4 production suites ~12 runs per year per suite ~50 patients per run 2,400 PATIENTS ANNUALLY 3 global production suites 8 automated units per suite 100 patients per unit per year
2,400 PATIENTS ANNUALLY Illustrative
Two AVR-RD-01 Fabry clinical trials
9 patients dosed across Phases 1 and 2 PHASE 1 Investigator-Sponsored Trial* PHASE 2 AVRO - FAB-201 Trial Patients Patients Key Objective Key Objectives n = 5 (fully enrolled) On ERT > 6 months prior to enrollment 18 - 50 year-old males n =
8-12 (4 patients dosed to-date) Treatment-naive 16 - 50 year-old males Safety and preliminary efficacy Safety and efficacy July 2019 data presented, unless otherwise specified * Sponsored by FACTs team (Fabry Disease Clinical Research and
Therapeutics) in Canada
FAB-201 Patient 1: 87% substrate
reduction in kidney biopsy Average number of Gb3 inclusions per peritubular capillary (PTC) Baseline 1 Year (48 weeks) Baseline: The last available, non-missing observation prior to AVR-RD-01 infusion Note: With respect to Fabry disease, Gb3
inclusions per PTC is interchangeable with GL-3 inclusions per KIC FAB-201-1: First patient in FAB-201 clinical trial 3.55 0.47 Unpaired t test for difference between n=55 PTCs at baseline vs. n=101 PTCs at 1 year; p < 0.0001 Error bar represents
the standard deviation 3.55
KIDNEY FUNCTION remains within
normal range FAB-201 Patient 1: Kidney and cardiac function stable at one year CARDIAC FUNCTION remains within normal range Reference Range Mean Values SD EF (%) LVM (g) LVMI (g/m2) Male (20-39 years) 64.3 4.2 138.9 24.5 67.8
10.7 mGFR mL/min/1.73 m2 eGFR mL/min/1.73 m2 EF (%) LV Mass (Absolute) (g) LV Mass Index (Normalized) (g/m2) Normal Range mGFR/eGFR Male (20-29 years) Average 116* Source: https://www.kidney.org/atoz/content/gfr Note: mGFR is measured
Glomerular Filtration Rate; eGFR is estimated Glomerular Filtration Rate Source: Alfakih K et al, J Magn Reson Imaging, 2003 Note: EF is Ejection Fraction; LVMI is Left Ventricular Mass Index
Gene Therapy FAB-201 Patient 1:
Substantial reduction in plasma substrate / metabolite levels, sustained at 1 year Plasma Lyso-Gb3 87% Reduction Plasma Gb3 73% Reduction Gene Therapy Infuse AVR-RD-01 Day 0 Baseline: The last available, non-missing observation prior to AVR-RD-01
infusion Note: AVR-RD-01 is an investigational gene therapy nM nM Infuse AVR-RD-01 Day 0
Anti-AGA antibodies Transient low
titer in 1 subject (resolved) AEs and SAEs reported AEs Generally consistent with myeloablative conditioning, underlying disease or pre-existing conditions SAEs Pre-treatment Seizure (resolved) Post-treatment Dehydration, nausea, vomiting (resolved)
Febrile neutropenia (resolved) FAB-201 No unexpected trends or safety events identified No AEs or SAEs related to AVR-RD-01 drug product Note: Safety database cut as of July 10, 2019 for the first 3 patients dosed
Two AVR-RD-01 Fabry clinical trials
9 patients dosed across Phases 1 and 2 PHASE 1 Investigator-Sponsored Trial* Patients Patients Key Objective Key Objectives n = 5 (fully enrolled) On ERT > 6 months prior to enrollment 18 - 50 year-old males n = 8-12 (4 patients dosed to-date)
Treatment-naive 16 - 50 year-old males Safety and preliminary efficacy Safety and efficacy * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada PHASE 2 AVRO - FAB-201 Trial
Phase 1: Plasma lyso-Gb3 reduction
sustained >2 yrs Reduced 41% from ERT baseline* ERT No ERT Gene Rx ERT + Gene Therapy Gene Therapy Infuse AVR-RD-01 ERT Discontinued ERT-Lyso-Gb3 Range *Baseline: The mean of the values reported prior to initiating mobilization Note:
AVR-RD-01 is an investigational gene therapy candidate Day 0 18 Mo Patient #1
Phase 1: Plasma lyso-Gb3
consistently reduced by 33-41% vs. baseline* ERT at 6+ months post AVR-RD-01 treatment PATIENT 1 - OFF ERT 41% Reduction PATIENT 3 - OFF ERT 41% Reduction PATIENT 2 - ON ERT 38% Reduction ERT Lyso-Gb3 Range Baseline PATIENT 4
- ON ERT** 33% Reduction *Baseline: The mean of the values reported prior to initiating mobilization Percent reduction: As measured from baseline to last assessment **Patient 4 discontinued ERT 7 months after gene therapy dose ERT
Lyso-Gb3 Range ERT Lyso-Gb3 Range ERT Lyso-Gb3 Range
Phase 1: Leukocyte and plasma enzyme
activity sustained >2 years; VCN stable VCN Infuse AVR-RD-01 Day 0 Plasma AGA Activity (nmol/hr/mL) Leukocyte AGA Activity (nmoles/hr/mg) VCN (per cell) Plasma AGA Activity Leukocyte AGA Activity Patient #1 Infuse AVR-RD-01 Day 0 Note: 0.1 VCN is
indicative of approx. 5-10% of all nucleated cells having an average of 1-2 copies of the transgene
Phase 1: Leukocyte and plasma enzyme
activity levels trend consistently across all patients Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Day 0 Infuse AVR-RD-01 Day 0 Note: Enzyme measurements are taken at ERT troughs; Note: Dotted line illustrative only Patient #5's Day 12
data point was utilized since the one month data was not obtained 28 Mo
Investigator-sponsored* Phase 1/2
study in Cystinosis OBJECTIVES PATIENTS ASSESS Safety Efficacy 6 patients Adults and potentially adolescents 14-17 years old Using oral and ophthalmic cysteamine Cystine levels in granulocytes Vector Copy Number (VCN) Chimerism Renal,
respiratory and endocrine function, ophthalmologic findings, muscle strength, growth, bone density, neurologic and psychometric measures Safety A Phase 1/2 study to determine the safety and efficacy of transplantation with autologous human CD34+
Hematopoietic Stem Cells (HSC) from Mobilized Peripheral Blood Stem Cells (PBSC) of patients with Cystinosis modified by ex vivo transduction using the pCCL-CTNS lentiviral vector Weeks 6-14 Months 6, 12, 18 & 24 Safety & efficacy
assessments Day -140 Discontinue cysteamine eye drops Day -70 Mobilize stem cells Day -20 Discontinue oral cysteamine Day -5 Conditioning Day 0 Infuse AVR-RD-04 Day 28 Post-treatment assessment CYSTINOSIS PATIENTS * Sponsored by UCSD
Cystinosis is a serious, underserved
rare disease Current treatment options are inadequate, burdensome, and treat symptoms only Standard of care cysteamine (a cystine-depleting therapy) delays, but does not halt, progression to end-stage renal disease Significant compliance challenges
due to: Frequency of dosing (Cystagon 4x per day, Procysbi 2x per day, hourly eye drops) Side effects, including bad breath and skin odor Corneal cystine crystals Excessive thirst, Dehydration, hypothyroidism Elevated cystine in white blood cells
Fanconi syndrome, kidney failure Excessive urination Failure to thrive, rickets Most common inherited cause of renal Fanconi syndrome (onset of symptoms by 6-12 months of age) Overall incidence ranges from 1 in 100,000 to 200,000 newborns 2,000
patients estimated worldwide; 500 to 600 patients estimated in the U.S. Sources: Wilmer MJ et al, Pediatr Nephrol, 2011, National Institutes of Health, Horizon Therapeutics plc
NORMAL LYSOSOME CYSTINOSIS LYSOSOME
Cystinosis caused by defective gene that encodes cystinosin, an exporter protein Cysteine (monomer of cystine) Cystine (dimer) Functional exporter protein (Cystinosin) Defective exporter protein (Cystinosin) Cystine crystals Causes cystine crystals
to build up in lysosomes, leading to tissue and organ damage
GAU-201: Phase 1/2 study in Gaucher