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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 dur

Key Takeaway: Company Presentation April 3, 2020 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 r

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Company Presentation April 3, 2020
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, the potential impact of the COVID-19 outbreak on our
clinical trial programs and business generally, as well as our plans and expectations with respect to the timing and resumption of any development activities that may be temporarily paused as a result of the COVID-19 outbreak, 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, 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, including the features of our plato
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, risks relating to clinical trial and business
interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our development timeline and/or increase our development costs or that data collection efforts may be impaired
or otherwise impacted by such crises, 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 Annual Report on Form 10-K, 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. Note regarding future updates: The statements contained
in this presentation reflect our current views with respect to future evets, which may change significantly as the global consequences of the COVID-19 pandemic rapidly develop. Accordingly, we do not undertake and specifically disclaim any
obligation to update any forward-looking statements.
Our mission: Giving people with genetic
disease freedom for life
GAUCHER "Bone pain feels like
gut-wrenching spikes. If I breathe, it goes away. But you can't make a bone crisis go away." "We need to help people understand the invisible' devastating pain and fatigue caused by this disease." FABRY
CYSTINOSIS "My mom kind of explained: we have a tsunami in the back and a tornado in the front when I'm 40 or 50 years old, who knows how healthy I will be? I may not be strong, I may not be able to [do] my job."
Multiple programs in the clinic
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 Phase 2 Phase 1/2 Phase 1/2 10 patients dosed to date IND:
Investigational New Drug
Addressing multi-billion dollar market
opportunity Disease Est. Cost Per Patient Per Year Approx. 2019 Net Sales Selected Companies Fabry $1.4B Gaucher $1.4B Pompe $1.0B 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; 2019 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
Lifelong treatments vs. potential
single-dose therapy Treatment burden Enzyme or protein level DISEASE PROGRESSION CONTINUES DISEASE PROGRESSION COULD HALT OR REVERSE 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 Designed for 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 ERT: Enzyme Replacement Therapy; IV: Intravenous; HSC: Hematopoietic Stem Cells
Established ex vivo lentiviral approach
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
Fabry Disease AVR-RD-01
Goals for gene therapy in Fabry
disease UNMET NEEDS: Kidney function Unmet needs: proteinuria, polyuria, kidney failure Cardiac function Unmet needs: left ventricular hypertrophy, fibrosis, heart failure Neuropathic pain Unmet needs: pain and burning sensations in hands and feet,
pain crises Everyday burden of illness and life expectancy Unmet needs: fatigue, inability to sweat, joint pain, abdominal pain, diarrhea, vomiting, cloudy vision, hearing loss, tinnitus, rash, angiokeratomas, biweekly infusions, shortened lifespan
CNS complications Unmet needs: TIA/stroke, depression, impaired executive function, white matter hyperintensities Sources: Wanner C et al, Med Genetics and Metab, 2018; Burlina A, JIEMS, 2016 CNS: Central Nervous System; TIA: Transient Ischemic
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
PATIENT 1 PATIENT 2 PATIENT 3
PATIENT 4 Age of symptom onset / diagnosis 10 / 19 years 36 / 37 years 13 / 13 years 9 / 9 years Age dosed with AVR-RD-01 21 years 46 years 40 years 26 years Mutation c.1021G>A (p.E341K) c.644A>G (p.N215S) c.639+1G>T c.833dupA 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 Chronic pain Peripheral neuropathy Neuropathic shuffling gait Lethargy Temperature intolerance Tinnitus Hearing loss GI
symptoms Leukocyte AGA enzyme activity at baseline (nmol/hr/mg protein) 0.10* 2.38** 0.58** 0.46** Plasma lyso-Gb3 at baseline (nM) 202*** 8*** 147*** 92*** Comment IgA deposits in kidney biopsy Cardiac variant, not a classic Fabry male Fabry
FAB-201 Patient Characteristics Treatment-na ve Fabry patients * Mayo Lab, ref range 23.1 nmol/hr/mg ** Rupar Lab, ref range 24-56 nmol/hr/mg *** Reference value 2.4 nM AGA: galactosidase A; Lyso-Gb3:
Globotriaosylsphingosine; GI: Gastrointestinal; IgA: Immunoglobulin-A
Patient 1: 87% substrate reduction
in kidney biopsy at 1 year Average number of Gb3 inclusions per peritubular capillary (PTC) Baseline 1 Year (48 weeks) 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 Mean Number of Gb3 Inclusions per PTC 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 PTC: Peritubular Capillary; Gb3: Globotriaosylceramide; GL-3: Globotriaosylceramide; KIC: Kidney Interstitial Capillary FAB-201 FABRY PHASE 2
Infuse AVR-RD-01 Day 0 Infuse
AVR-RD-01 Day 0 *Lab A: Mayo Clinic Laboratories; Lab B: Rupar Laboratory; Lab A Reference Range: >23.1 nmol/hr/mg; Lab B Reference Range: 24-56 nmol/hr/mg Reference Range: 5.1-9.2 nmol/hr/mL AGA: -galactosidase A Patient
1: Multiple data trends sustained up to 18 months Leukocyte + Plasma AGA Enzyme Activity Leukocyte AGA (nmol/hr/mg protein)* Plasma AGA (nmol/hr/mL protein) Drug Product VCN: 0.7 Vector Copy Number (VCN) VCN/Diploid Genome - PBMCs VCN:
Vector Copy Number; PBMCs: Peripheral Blood Mononuclear Cells KIDNEY FUNCTION remains within normal range at 12 mos. CARDIAC FUNCTION remains within normal range at 12 mos. mGFR mL/min/1.73 m2 eGFR mL/min/1.73 m2 EF (%) LV Mass (Absolute) (g) LV
Mass Index (Normalized) (g/m2) Baseline Month 12 *Source: https://www.kidney.org/atoz/content/gfr mGFR: Measured Glomerular Filtration Rate; eGFR: Estimated Glomerular Filtration Rate Source: Alfakih K et al, J Magn Reson Imaging, 2003 EF: Ejection
Fraction; LV: Left Ventricular Normal Range mGFR/eGFR Average 116* mL/min/1.73 m2 Male (20-39 years) Reference Range Mean Values SD 64.3 4.2% 138.9 24.5 g 67.8 10.7 g/m2 Male (20-39 years) Baseline Month 12
Infuse AVR-RD-01 Day 0 Plasma AGA Missing Plasma AGA Analysis Leukocyte AGA (Lab B) Leukocyte AGA (Lab A) Lyso-Gb3, Plasma (nM)* Total Gb3 Lyso-Gb3 Plasma Lyso-Gb3 and Total Gb3 Total Gb3, Plasma (nM) *Reference Value: 2.4 nM Reference
Value: 4961 nM; 6012 nM before August 2018 (until Day 28 for Patient 1) Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Note: Patient #1 had a skin biopsy score of 3 (severe accumulation) at baseline, a score of 2 (moderate
accumulation) at 6 months and a score of 1 (mild accumulation) at 12 months FAB-201 FABRY PHASE 2
Patient 2: Multiple data trends
sustained up to 12 months Plasma AGA Leukocyte AGA Drug Product VCN: 0.5 VCN: Vector Copy Number; PBMCs: Peripheral Blood Mononuclear Cells *Data from Rupar Laboratory; Reference Range: 24-56 nmol/hr/mg Reference Range: 5.1-9.2
nmol/hr/mL AGA: -galactosidase A Infuse AVR-RD-01 Day 0 KIDNEY FUNCTION remains within normal range mGFR mL/min/1.73 m2 eGFR mL/min/1.73 m2 EF (%) LV Mass (Absolute) (g) LV Mass Index (Normalized) (g/m2) Baseline Month 12 Source:
https://www.kidney.org/atoz/content/gfr mGFR: Measured Glomerular Filtration Rate; eGFR: Estimated Glomerular Filtration Rate Source: Alfakih K et al, J Magn Reson Imaging, 2003 EF: Ejection Fraction; LV: Left Ventricular Reference Range Mean Values
Male 40-49 years 55-65% 58-91 g/m2 Baseline Month 12 Normal Range mGFR/eGFR Average 99 mL/min/1.73 m2 Male (40-49 years) CARDIAC FUNCTION remains within normal range Infuse AVR-RD-01 Day 0 Total Gb3 Lyso-Gb3 *Reference Value: 2.4
nM; Reference Value: 4961 nM Note: Patient #2 has normal substrate, consistent with late-onset cardiac variant phenotype Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Infuse AVR-RD-01 Day 0 Note: As patient #2 is a cardiac
variant of Fabry disease, this patient had a skin biopsy score of 0 (trace or no accumulation) at baseline and at 6 months Leukocyte + Plasma AGA Enzyme Activity Vector Copy Number (VCN) Plasma Lyso-Gb3 and Total Gb3 Leukocyte AGA (nmol/hr/mg
protein)* Plasma AGA (nmol/hr/mL protein) VCN/Diploid Genome - PBMCs Lyso-Gb3, Plasma (nM)* Total Gb3, Plasma (nM) FAB-201 FABRY PHASE 2 - Cardiac Variant
Drug Product VCN: 1.4 VCN/Diploid
Genome - PBMCs Leukocyte + Plasma AGA Enzyme Activity Vector Copy Number (VCN) Leukocyte AGA (nmol/hr/mg protein)* Plasma AGA (nmol/hr/mL protein) Plasma AGA Leukocyte AGA *Data from Rupar Laboratory; Reference Range: 24-56
nmol/hr/mg Reference Range: 5.1-9.2 nmol/hr/mL AGA: -galactosidase A VCN: Vector Copy Number; PBMCs: Peripheral Blood Mononuclear Cells Infuse AVR-RD-01 Day 0 Plasma Lyso-Gb3 and Total Gb3 Lyso-Gb3, Plasma (nM)* Total Gb3, Plasma
(nM) Total Gb3 Lyso-Gb3 *Reference Value: 2.4 nM Reference Value: 4961 nM Lyso-Gb3: Globotriaosylsphingosine; Gb3: Globotriaosylceramide Infuse AVR-RD-01 Day 0 Infuse AVR-RD-01 Day 0 Skin Biopsy Score (Patient 3) Baseline 2 6 months 2
Plasma AGA Enzyme Activity Infuse AVR-RD-01 Day 0 Patient 3: Initial divergent profile with 9 month data trending toward anticipated long-term engraftment FAB-201 FABRY PHASE 2
Two AVR-RD-01 Fabry clinical trials
PHASE 1 Investigator-Sponsored Trial* Patients Patients Key Objectives 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 PHASE 2 AVRO - FAB-201 Trial 9 patients dosed across Phases 1 and 2 FAB-201 = AVRO-RD-01-201 Study * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada ERT:
Enzyme Replacement Therapy
PATIENT 1 PATIENT 2 PATIENT 3
PATIENT 4 PATIENT 5 Age of symptom onset / diagnosis 18 / 37 years 9 / 29 years 10 / 0 years 7 / 4 years 10 / 14 years Years on ERT 11 years 6 years 4 years 11 years 2 years Age dosed with AVR-RD-01 48 years 39 years 40 years 37 years 30 years
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/hr/mg protein) 2.1* 1.1* 0.6* 2.2* 1.0* Plasma lyso-Gb3 at baseline (nM) 25**
26** 59** 29** 16** ERT discontinuation status 18 months after gene therapy dose Did not resume ERT after gene therapy dose 6 months after gene therapy dose Fabry Phase 1 Patient Characteristics ERT-Treated Fabry Patients * Rupar Lab, ref range
24-56 nmol/hr/mg ** Reference value 2.4 nM Note: AGA: galactosidase A; ERT: Enzyme Replacement Therapy; GI: Gastrointestinal; Lyso-Gb3: Globotriaosylsphingosine
Patients 1-5: Plasma lyso-Gb3
Last updated: Apr 3, 2020