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Freedom from a lifetime of disease
Corporate Presentation October 2019 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 such
as "aims," "anticipates," "believes," "could," "estimates," "expects," "forecasts", "goal," "intends," "may" "plans,"
"possible," "potential," "seeks," "will," and variations of these words 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, 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, 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 our investigational gene therapies. 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.
Deep pipeline targeting lysosomal
storage disorders (LSDs) where SoC ~$4B 2018 net sales Compelling Fabry data across Phase 1 and Phase 2 trials Gaucher and cystinosis trial recruitment underway Powered by plato - our commercial-stage manufacturing platform Management
comprised of cell, gene and rare disease industry leaders Multiple near-term milestones anticipated Developing gene therapies designed to cure rare diseases
Cell, gene and rare disease industry
leaders MANAGEMENT TEAM BOARD OF DIRECTORS Geoff MacKay President and CEO Kim Warren, PhD Head of Operations Chris Mason, MD, PhD, FRCS Chief Science Officer Deanna Petersen, MBA Chief Business Officer Kathryn McNaughton, PhD SVP Portfolio &
Program Management Birgitte Volck, PhD, MD President of Research and Development Erik Ostrowski Chief Financial Officer Steven Avruch, JD General Counsel Josie Yang, PhD Head of Regulatory Affairs Bruce Booth, DPhil Chairman Ian Clark Philip
Vickers, PhD Annalisa Jenkins, MBBS, FRCP Phillip Donenberg Chris Paige, PhD Geoff MacKay Georgette Verdin Chief Human Resources Officer
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 4 clinical trials up and running Phase 1 Phase 2 Phase 1/2
Phase 1/2 Pre-Clinical
Addressing multi-billion dollar markets
Disease Est. Cost 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 $625k-700k
Life-long treatments vs. potential
single dose cure Treatment burden Enzyme or protein level DISEASE PROGRESSION CONTINUES DISEASE PROGRESSION COULD HALT Enzyme Replacement Therapy (ERT) Temporary bolus of enzyme, not curative Bi-Weekly ERT Plasma Pharmacokinetics of ERT Life-long
infusions Transient, intermittent elevation Bi-weekly IV infusions AVROBIO Gene Therapy 24/7 expression of protein, curative potential Functional Protein Expression in Transduced HSCs and Their Progeny 24/7 expression One-Time Gene Therapy
Long-term, continuous elevation Single IV infusion
One platform applied across our
portfolio Transduce with lentiviral vector carrying normal gene GENE THERAPY PLATFORM Select CD34+ stem cells Collect mobilized blood 3 2 1 Harvest and freeze 4 Infuse 5
Endogenous enzyme delivered to tissues
via multiple cell lineages Long-term engraftment in bone marrow Manufacturing, transportation and delivery in blood Example target organ T NK B RBC Platelets Granulocytes DC Monocytes Kidney glomerulus LEUKOCYTES
Two AVR-RD-01 Fabry clinical trials
8 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 (3 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
FAB-201 Primary and secondary
endpoints FAB-201 Primary efficacy endpoint Average number of Gb3 inclusions per kidney peritubular capillary (PTC) Biopsy at 1 year vs. baseline FDA-recognized endpoint in Fabry BIOMARKERS Toxic metabolite - lyso-Gb3 in plasma, urine
Substrate - Gb3 in plasma, urine, skin Enzyme - AGA in leukocytes, plasma VCN PATIENT WELL-BEING Clinical status Quality of life ORGAN AND SYSTEM FUNCTION Kidney function Cardiac function GI distress Pain Secondary efficacy endpoints
Gb3, also referred to as GL-3: a type of fat that builds in cells, resulting in damage to kidneys, heart and brain Peritubular capillaries (PTCs), also referred to as kidney interstitial capillaries (KICs) convey blood after filtration in the
glomeruli, enabling it to eventually exit the kidneys and return to the circulatory system AEs, SAEs Clinical labs, ECG, vital signs Antibodies, RCL, ISA Primary safety endpoints
PATIENT 1 PATIENT 2 PATIENT 3 Age
symptom onset / diagnosis 10 / 19 years 36 / 37 years 13 / 13 years Age dosed with AVR-RD-01 21 years 46 years 40 years Mutation c.1021G>A (p.E341K) c.644A>G (p.N215S) c.639+1G>T Primary disease signs and symptoms Kidney disease Chronic
pain GI symptoms Decreased cold sensation Cardiac disease Peripheral neuropathy Chronic pain Increased tiredness GI symptoms Intermittent tinnitus Mild high frequency hearing loss Raynaud's syndrome Kidney disease GI symptoms Peripheral
neuropathy Bilateral deafness Tinnitus Peripheral edema Decreased cold sensation Leukocyte AGA enzyme activity at baseline (nmol/h/mg) 0.10* 2.38** 0.58** Plasma lyso-Gb3 at baseline (nM)*** 202 8 147 Comment IgA deposits in kidney biopsy Cardiac
variant, not a classic Fabry male FAB-201 Patient Characteristics * Mayo Lab, ref range 23.1 nmol/h/mg ** Rupar Lab, ref range 24-56 nmol/h/mg *** Reference value 2.4 nM
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
FAB-201 Patient 1: Continued
reduction in substrate inclusions in skin endothelial cells Source: Thurberg BL, 2011, https://everylifefoundation.org/wp-content/uploads/images/workshopseries/16-Thurberg-Fabry-pathology-Nov-2011-compr-dc.pdf Severe accumulation Mild accumulation
Moderate accumulation Biopsy Score Baseline Month 6 Month 12 Trace or no accumulation
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
FAB-201 Patient 1: Sustained
leukocyte and plasma enzyme activity at 1 year; VCN stable Infuse AVR-RD-01 Day 0 Plasma AGA Activity Plasma AGA Activity (nmol/hr/mL) Leukocyte AGA Activity (nmoles/hr/mg) Day 0 VCN VCN (per cell) Leukocyte AGA Activity Infuse AVR-RD-01 Note: 0.1
VCN is indicative of approx. 5-10% of all nucleated cells having an average of 1-2 copies of the transgene Baseline: The last available, non-missing observation prior to AVR-RD-01 infusion
FAB-201 Patient 2: Sustained
leukocyte and plasma enzyme activity and VCN at 6 months Day 0 VCN Leukocyte AGA Activity Plasma AGA Activity Infuse AVR-RD-01 Day 0 Infuse AVR-RD-01 Plasma AGA Activity (nmol/hr/mL) Leukocyte AGA Activity (nmoles/hr/mg) VCN (per cell) Note: Patient
3 had plasma AGA activity of 0.740, leukocyte AGA activity of 9.94 and VCN of 0.12 as of 1 month Note: 0.1 VCN is indicative of approx. 5-10% of all nucleated cells having an average of 1-2 copies of the transgene Baseline: The last available,
non-missing observation prior to AVR-RD-01 infusion
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 3 patients dosed 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
Two AVR-RD-01 Fabry clinical trials
8 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 (3 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 Patient Characteristics
PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 PATIENT 5 Age symptom onset / diagnosis 18 / 37 9 / 29 10 / 0 7 / 4 10 / 14 Years on ERT 11 6 4 11 2 Age dosed with AVR-RD-01 48 39 40 37 30 Mutation c.962A>G (p.Q321R) c.1033T>C (p.S345P) c.427G>C
(p.A143P) c.427G>C (p.A143P) (p.Y134S) Primary disease signs and symptoms Kidney disease Cardiac disease GI pain GI diarrhea Angiokeratoma Insomnia Kidney disease Cardiomyopathy Hypohidrosis Corneal verticillata Peripheral neuropathy GI symptoms
Angiokeratoma Lymphedema Acroparesthesia Cardiac Disease Tinnitus Headaches Dizziness Acroparesthesia Cardiac Disease Hypohidrosis Tinnitus Corneal verticillata Angiokeratoma GI symptoms Kidney disease Hypertension Hypohidrosis Tinnitus Migraines
Impaired hearing Angiokeratoma Sleep apnea Asthma Depression Leukocyte AGA activity at baseline* (nmol/h/mg) 2.1 1.1 0.6 2.2 1.0 Plasma lyso-Gb3 at baseline (nM)** 25 26 59 29 16 Discontinued ERT 18 months after gene therapy dose Did not resume ERT
after gene therapy dose 7 months after gene therapy dose * Rupar Lab, ref range 24-56 nmol/h/mg ** Reference value 2.4 nM
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